WO2003022257A1 - External preparations for the skin - Google Patents

External preparations for the skin Download PDF

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Publication number
WO2003022257A1
WO2003022257A1 PCT/JP2002/009270 JP0209270W WO03022257A1 WO 2003022257 A1 WO2003022257 A1 WO 2003022257A1 JP 0209270 W JP0209270 W JP 0209270W WO 03022257 A1 WO03022257 A1 WO 03022257A1
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WIPO (PCT)
Prior art keywords
skin
external preparation
cedrol
component
salts
Prior art date
Application number
PCT/JP2002/009270
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French (fr)
Japanese (ja)
Inventor
Atsushi Suzumatsu
Hikaru Sumida
Toshio Uesaka
Kimihiko Hori
Mami Nonomura
Original Assignee
Kao Corporation
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Publication of WO2003022257A1 publication Critical patent/WO2003022257A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/342Alcohols having more than seven atoms in an unbroken chain
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • A61K2800/75Anti-irritant

Definitions

  • the present invention relates to an external preparation for skin which has improved percutaneous absorbability of cedrol, and has excellent anti-inflammatory, anti-allergic (IL 4 production inhibition) and irritation-relieving effects.
  • Drug administration methods include oral administration, mucosal administration, injection administration, and other methods of directly administering the drug into the body. Recently, topical preparations containing these drugs by transdermal administration have been developed because of their low side effects.
  • the surface of the skin is covered by the stratum corneum and has a structure that prevents foreign substances from entering from outside the body.
  • Simply applying an external preparation containing an active ingredient to the epidermis is sufficient for transdermal absorption You can't get to life.
  • transdermal absorption enhancers such as dimethyl sulfoxide, dimethylformamide, and dimethylacetamide have been proposed (Japanese Patent Application Laid-Open No. Sho 61-331129).
  • these transdermal absorption enhancers were not sufficient in terms of irritation, stability, and feeling of use.
  • Sedokuru has an excellent anti-inflammatory and anti-allergic effect due to an excellent inhibitory effect on IL 4 production (Japanese Patent Application Laid-Open No. 2000-3099528). Since it is an insoluble substance, transdermal absorption of cedrol into the stratum corneum was often not sufficient.
  • An object of the present invention is to provide an external preparation for skin in which the transdermal absorbability of cedrol is improved and the effects of cedrol (anti-inflammatory action, anti-allergic action, irritation-relieving action) can be sufficiently exerted. Disclosure of the invention
  • the present inventor uses the softening action of the stratum corneum possessed by the a-on surfactant and the compatibility between the anionic surfactant and cedrol to efficiently store cedrol in the stratum corneum. It has been found that a skin external preparation with improved percutaneous absorption and biotransformation can be obtained. In addition, by using one or more anionic surfactants having a phosphate ester group or an acylamino group as anionic surfactants that are satisfactory in terms of safety and usability, the transdermal absorption of cedrol It has been found that an external preparation for skin can be obtained that further enhances the anti-inflammatory action, anti-allergic action (suppressing IL-4 production) and irritation-relieving action of cedrol itself.
  • the present invention comprises the following components (A) and (B):
  • Cedrol of component (A) used in the external preparation for skin of the present invention is a kind of sesquiterpene alcohol, and has an optical isomer, but is generally represented by the formula (1) (d) Exists in the body.
  • Cedrol which is an active ingredient having an antiallergic effect according to the present invention, is preferably the (d) isomer, but is an optical isomer of the (1) isomer or a mixture of the (d) isomer and the (1) isomer However, there is no problem in effectiveness.
  • Cedrol is generally known as a fragrance component contained in essential oils of plants such as Pinaceae, Cedars, Cypresses, Scorpiones, Prunus, etc. It can be obtained by purifying essential oils such as fern wood oil and hiba oil by distillation or the like, and can also be obtained by synthesis. As the cedrol used in the present invention, any of the above-mentioned essential oil products and synthetic products may be used, or a commercially available product may be used.
  • cedrol is contained in the skin preparation for external use of the present invention in an amount of 0.01 to 10% by weight, particularly 0.1 to 5% by weight, the anti-inflammatory and anti-allergic effects can be effectively exhibited. preferable.
  • anionic surfactant of the component (B) used in the skin external preparation of the present invention examples include those having a phosphate group, an acylamino group, a carboxylic acid group, a sulfonic acid group, a sulfate ester group, and the like, and salts thereof. No.
  • phosphate ester group examples include alkyl phosphates and alkyl ether phosphates; those having an acylamino group include acylsarcosine, acylglutamate, acylmethyltaurine, and acylalginate.
  • Carboxylic acid groups such as fatty acid salts, ether carboxylic acids or salts thereof; sulfonic acid groups, such as alkyl sulfonates, sulfosuccinates, and ester sulfonates.
  • alkylaryl sulfonates examples of those having a sulfate group include sulfated oils, ester sulfates, alkyl sulfates, ether sulfates, and alkylaryl sulfates.
  • 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 salt, monoethanolamine salt, and diethanolamine salt. Preferred are alkali metal salts.
  • the alkyl 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.
  • an ionic surfactant having a phosphate ester group and an anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms have no skin irritation and a feeling of use. From the viewpoint, it is more preferable in terms of the transdermal absorption effect.
  • Specific examples include sodium monolauryl phosphate, sodium isostearyl phosphate, 21-hexyl decyl phosphate arginine, 21-heptyl pentadecyl phosphate, polyoxyethylene (4 to 10) lauryl ether phosphorus Sodium acid, sodium monocetyl phosphate, monomyristinolelate anoreginine, sodium monooleate, polyoxyethylene (2 to 10) lauryl ether 02 09270 Potassium phosphate, sodium octyl phosphate and the like.
  • anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms examples include N—C 14 to C 24 acyl sarcosine salts, N—C 14 to C 24 acyl methyl taurine salts, and N—C 14 -C 24 ⁇ sill glutamate, N- C 14 ⁇ C 24 ⁇ sills arginine salt, N_ C 14 ⁇ C 24 ⁇ sill methyl ⁇ La Nin salts.
  • the anionic surfactant is preferably contained in the skin external preparation in an amount of 0.001 to 10% by weight, particularly 0.1 to 5% by weight, in view of the effect and stability.
  • the skin external preparation of the present invention may be a component usually used in skin external preparations such as pharmaceuticals, quasi-drugs, and cosmetics, for example, whitening agents, humectants, Inhibitors, UV absorbers, nonionic surfactants (polyoxyethylene hydrogenated castor oil, etc.), oily components (scoulane, olive oil, higher alcohols, higher fatty acids, etc.), thickeners (hydroxyethyl cellulose, xanthan gum, carboxy) Vinyl alcohols), alcohols (glycerin, 1,3-butylendalcol, ethanol, etc.), organic acids (cunic acid, succinic acid, adipic acid, lactic acid), pH adjusters (sodium hydroxide) , Potassium hydroxide, etc.), powder components, coloring agents, aqueous components, preservatives, antioxidants, fragrances, chelating agents, water, various skin nutrition agents, crude drugs, extracts, It may be
  • the external preparation for skin of the present invention can be produced according to a usual method, and can be in the form of, for example, a cream, an emulsion, a lotion, a jewel, and the like.
  • a skin external preparation having the following composition was prepared by a conventional method, and evaluated for percutaneous absorption, irritation, and feeling upon use. Table 1 shows the results. 02 09270
  • composition Cedrol 0.1 (% by weight)
  • a patch test patch having a hole diameter of 16 ram was applied to the upper arm of the panelists (10 persons), and 200 L of the sample was applied. After the application, the banso plaster was peeled off for 6 hours, and in the next step, the application portion was tape-striped 10 times with a velcro tape to measure the amount of cedrol in the stratum corneum adhered to the cellophane tape.
  • cedrol The quantitative determination of cedrol was performed by gas chromatography using ethanol extract from 10 cellophane tapes.
  • the percutaneous absorption rate was determined by the following formula, and was determined according to the criteria.
  • Amount of cedrol applied Percutaneous absorption criteria 1; Percutaneous absorption less than 1%
  • Irritation criteria A; Number of people who felt a little irritation 0 people
  • Example 2 (Emulsion) Cedrol 0. Polyoxyethylene (4) sodium lauryl ether phosphate 0.3 N-Stearoyl-N-methyltadulin sodium 1 Sorbitan monostearate 0.3 Olive oil 2.5
  • Methyl polysiloxane 6cs
  • Polyoxyethylene 60
  • Hardened castor oil 60
  • Hardened castor oil 60
  • Glycerin 60
  • Trimethyldaricin 2
  • Acrylic acid 66
  • the skin external preparations of Examples 2 to 5 are excellent in percutaneous absorbability of cedrol, and are excellent in anti-inflammatory, anti-allergic (suppressing IL-4 production), stimulating alleviation, and feeling of use. Good. Industrial availability
  • the external preparation for skin of the present invention improves the transdermal absorbability of cedrol, is excellent in anti-inflammatory action, anti-allergic (IL4 production inhibition) action, irritation relieving action, and has good feeling in use.

Abstract

External preparations for the skin which contain the following components (A) and (B): (A) cedrol; and (B) an anionic surfactant. These preparations show improved percutaneous absorbability of cedrol and excellent antiinflammatory, antiallergic (regulating IL4 production) and irritation-relieving effects and give a favorable feel in using.

Description

明細書 皮膚外用剤 技術分野  Description Skin external preparation Technical field
本発明は、 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 (I L 4産生抑制) 作用、 刺激緩和作用に優れた皮膚外用剤に関する。 背景技術  The present invention relates to an external preparation for skin which has improved percutaneous absorbability of cedrol, and has excellent anti-inflammatory, anti-allergic (IL 4 production inhibition) and irritation-relieving effects. Background art
薬剤の投与方法には、 経口投与、 粘膜への投与、 注射での投与等の薬剤を直接 体内へ投与する方法がある。 最近は副作用の少なさから、 経皮投与によるこれら 薬剤を含む外用製剤が開発されている。  Drug administration methods include oral administration, mucosal administration, injection administration, and other methods of directly administering the drug into the body. Recently, topical preparations containing these drugs by transdermal administration have been developed because of their low side effects.
一般に、 皮膚の表面 (表皮) は角質層に覆われ、 体外からの異物進入を阻止す る構造になっており、 単に有効成分を配合した外用剤を表皮に塗布しただけでは 十分な経皮吸収十生は得られない。 そこで表皮からの直接吸収を改良するために、 ジメチルスルホキシド、 ジメチルホルムアミド、 ジメチルァセトアミ ド等の経皮 吸収促進剤が提案されている (特開昭 6 1—3 3 1 2 9号) 。 し力 し、 これらの 経皮吸収促進剤は、刺激十生、安定性、使用感の面で十分であるとはいえなかった。 一方、 発明者らはセド口ールに優れた I L 4産生抑制作用による抗炎症作用、 抗アレルギー作用があることを見出した (特開 2 0 0 0— 3 0 9 5 2 8 ) 力 水 に不溶性の物質であり、 角質層内へのセドロールの経皮吸収性が十分とはいえな い場合が多かった。  In general, the surface of the skin (epidermis) is covered by the stratum corneum and has a structure that prevents foreign substances from entering from outside the body. Simply applying an external preparation containing an active ingredient to the epidermis is sufficient for transdermal absorption You can't get to life. In order to improve the direct absorption from the epidermis, transdermal absorption enhancers such as dimethyl sulfoxide, dimethylformamide, and dimethylacetamide have been proposed (Japanese Patent Application Laid-Open No. Sho 61-331129). However, these transdermal absorption enhancers were not sufficient in terms of irritation, stability, and feeling of use. On the other hand, the present inventors have found that Sedokuru has an excellent anti-inflammatory and anti-allergic effect due to an excellent inhibitory effect on IL 4 production (Japanese Patent Application Laid-Open No. 2000-3099528). Since it is an insoluble substance, transdermal absorption of cedrol into the stratum corneum was often not sufficient.
本発明の目的は、 セドロールの経皮吸収性が向上し、 セドロールの効果 (抗炎 症作用、 抗アレルギー作用、 刺激緩和作用) が十分に発揮できる皮膚外用剤を提 供することにある。 発明の開示  An object of the present invention is to provide an external preparation for skin in which the transdermal absorbability of cedrol is improved and the effects of cedrol (anti-inflammatory action, anti-allergic action, irritation-relieving action) can be sufficiently exerted. Disclosure of the invention
本発明者は、 ァ-オン界面活性剤の有する角質層軟化作用と、 ァニオン界面活 性剤とセドロールとの相溶性を利用し、 角質層内にセドロールを効率良く滞留さ せることで経皮吸収' ι·生が向上した皮膚外用剤が得られることを見出した。加えて、 安全性、 使用感の点で満足できるァニオン界面活性剤として、 リン酸エステル基 又はァシルァミノ基を有するァニオン界面活性剤を 1種ないし 2種以上用いるこ とで、 セドロールの経皮吸収性を優れたものにすると同時にセドロール自体の抗 炎症作用、 抗アレルギー (I L 4産生抑制) 作用、 刺激緩和作用を一段と高めた 皮膚外用剤が得られることを見出した。 The present inventor uses the softening action of the stratum corneum possessed by the a-on surfactant and the compatibility between the anionic surfactant and cedrol to efficiently store cedrol in the stratum corneum. It has been found that a skin external preparation with improved percutaneous absorption and biotransformation can be obtained. In addition, by using one or more anionic surfactants having a phosphate ester group or an acylamino group as anionic surfactants that are satisfactory in terms of safety and usability, the transdermal absorption of cedrol It has been found that an external preparation for skin can be obtained that further enhances the anti-inflammatory action, anti-allergic action (suppressing IL-4 production) and irritation-relieving action of cedrol itself.
本発明は、 次の成分 (A) 及び (B ) :  The present invention comprises the following components (A) and (B):
(A) セドローノレ、  (A) Sedronore,
(B ) ァニオン界面活性剤  (B) Anionic surfactant
を含有する皮膚外用剤を提供するものである。 発明を実施するための最良の形態 And a skin external preparation containing the same. BEST MODE FOR CARRYING OUT THE INVENTION
本発明の皮膚外用剤に使用する成分 (A) のセドロールは、 セスキテルペンァ ルコールの 1種であり、 光学異性体が存在するが、 一般的には式 ( 1 ) で示され る (d ) 体で存在する。 本発明の抗アレルギー作用の有効成分であるセドロール としては( d )体が^ましいが、光学異性体である ( 1 )体のもの、 もしくは( d ) 体と (1 ) 体の混在する形態であっても有効性に問題ない。  Cedrol of component (A) used in the external preparation for skin of the present invention is a kind of sesquiterpene alcohol, and has an optical isomer, but is generally represented by the formula (1) (d) Exists in the body. Cedrol, which is an active ingredient having an antiallergic effect according to the present invention, is preferably the (d) isomer, but is an optical isomer of the (1) isomer or a mixture of the (d) isomer and the (1) isomer However, there is no problem in effectiveness.
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、 ビヤク シン属、 クロべ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。 シダ 一ウッド油、 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、 また、 合成により得ることもできる。 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良く、 市販品を用いても良い。 Cedrol is generally known as a fragrance component contained in essential oils of plants such as Pinaceae, Cedars, Cypresses, Scorpiones, Prunus, etc. It can be obtained by purifying essential oils such as fern wood oil and hiba oil by distillation or the like, and can also be obtained by synthesis. As the cedrol used in the present invention, any of the above-mentioned essential oil products and synthetic products may be used, or a commercially available product may be used.
セドロールは、 本発明の皮膚外用剤中に 0 . 0 0 1〜 1 0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。 If cedrol is contained in the skin preparation for external use of the present invention in an amount of 0.01 to 10% by weight, particularly 0.1 to 5% by weight, the anti-inflammatory and anti-allergic effects can be effectively exhibited. preferable.
本発明の皮膚外用剤に使用する成分 (B ) のァニオン界面活性剤としては、 リ ン酸エステル基、 ァシルァミノ基、 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。  Examples of the anionic surfactant of the component (B) used in the skin external preparation of the present invention include those having a phosphate group, an acylamino group, a carboxylic acid group, a sulfonic acid group, a sulfate ester group, and the like, and salts thereof. No.
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;ァシルアミノ基を有するものとしては、 ァシルサルコシン塩、 ァ シルグルタミン酸塩、 ァシルメチルタウリン塩、 ァシルアルギ-ン塩、 ァシルメ チルァラニン塩等;カルボン酸基を有するものとしては、 脂肪酸石験、 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、 アルキルァリールスルホン 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、 ァ ルキル硫酸塩、 エーテル硫酸塩、 アルキルァリール硫酸塩等が挙げられる。 ここで、塩としては、ナトリゥム、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、 アンモニゥ 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、 ァ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 1 2以上、 ァシル基は炭素数 1 4以上が好ましい。  Those having a phosphate ester group include alkyl phosphates and alkyl ether phosphates; those having an acylamino group include acylsarcosine, acylglutamate, acylmethyltaurine, and acylalginate. Carboxylic acid groups, such as fatty acid salts, ether carboxylic acids or salts thereof; sulfonic acid groups, such as alkyl sulfonates, sulfosuccinates, and ester sulfonates. And alkylaryl sulfonates; examples of those having a sulfate group include sulfated oils, ester sulfates, alkyl sulfates, ether sulfates, and alkylaryl sulfates. 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 salt, monoethanolamine salt, and diethanolamine salt. Preferred are alkali metal salts. Further, among the above substituents containing an alkyl group and an 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.
成分 (B ) としては、 特にリン酸エステル基を有するァ-オン界面活性剤及ぴ 炭素数 1 4以上のァシル基を持つァシルアミノ基を有するァニオン界面活性剤力 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。  As the component (B), particularly, an ionic surfactant having a phosphate ester group and an anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms have no skin irritation and a feeling of use. From the viewpoint, it is more preferable in terms of the transdermal absorption effect.
リン酸エステル基を有するァ-オン界面活性剤としては、 モノ又はジ (C 6Mono- or di- (C 6- )
C24) アルキル又はナルケニルリン酸エステル塩、 モノ又はジ (ポリオキシェチ レン (2〜 2 0 ) C6〜C24アルキル又はァルケ-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、 2一へキシルデシルリン酸アルギニン、 2一へプチルゥンデシルリ ン酸カリウム、 ポリオキシエチレン (4〜 1 0 ) ラウリルエーテルリン酸ナトリ ゥム、 モノセチルリン酸ナトリゥム、 モノミリスチノレリン酸ァノレギニン、 モノォ レイルリン酸ナトリウム、 ポリオキシエチレン (2〜 1 0 ) ラウリルエーテルリ 02 09270 ン酸カリゥム、 ジォクチルリン酸ナトリゥム等が挙げられる。 C 24) alkyl or Narukenirurin ester salts, mono- or di (Poriokishechi Len (2~ 2 0) C 6 ~C 24 alkyl or Aruke - Le) phosphoric acid ester salts like et be. Specific examples include sodium monolauryl phosphate, sodium isostearyl phosphate, 21-hexyl decyl phosphate arginine, 21-heptyl pentadecyl phosphate, polyoxyethylene (4 to 10) lauryl ether phosphorus Sodium acid, sodium monocetyl phosphate, monomyristinolelate anoreginine, sodium monooleate, polyoxyethylene (2 to 10) lauryl ether 02 09270 Potassium phosphate, sodium octyl phosphate and the like.
炭素数 1 4以上のァシル基を持つァシルアミノ基を有するァニオン界面活性剤 としては、 N— C 14〜C24ァシルサルコシン塩、 N— C 14〜C24ァシルメチルタウリ ン塩、 N— C 14〜C24ァシルグルタミン酸塩、 N— C 14〜C 24ァシルアルギニン塩、 N_ C 14〜C24ァシルメチルァ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ゥム、 パルミトイルメチルタウリンナトリウム、 ス テアロイルメチル夕ゥリンナ卜リゥム、 N—ステアロイルグルタミン酸ナ卜リウ ム、 N—パルミトイルグルタミン酸カリウム、 N—パルミトイルー /3—ァラニン 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。 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 acyl methyl taurine salts, and N—C 14 -C 24 § sill glutamate, N- C 14 ~C 24 § sills arginine salt, N_ C 14 ~C 24 § sill methyl § La Nin salts. Specific examples include myristoyl methyl taurine sodium, palmitoyl methyl taurine sodium, stearoyl methyl phosphate sodium, sodium N-stearoyl glutamate, potassium N-palmitoyl glutamate, N-palmityl / 3-alanine arginine, palmitoyl Sarcosine sodium and the like.
本発明の皮膚外用剤には、 ァニオン界面活性剤は 2種以上を併用しても良い。 ァニオン界面活性剤は、 効果、 安定性の点で、 皮膚外用剤中に 0 . 0 0 1〜 1 0重量%、 特に 0 . 1〜 5重量%含有するのが好ましい。  In the skin external preparation of the present invention, two or more anionic surfactants may be used in combination. The anionic surfactant is preferably contained in the skin external preparation in an amount of 0.001 to 10% by weight, particularly 0.1 to 5% by weight, in view of the effect and stability.
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 (スクヮラン、 ォリーブ油、 高級アルコール、 高級脂肪酸等)、 増粘剤 (ヒドロキシェチルセルロース、 キサンタンガム、 カルボキシビニルポリ マ一等) 、 アルコール類 (グリセリン、 1 , 3—プチレンダリコール、 'ェタノ一 ル等) 、 有機酸類 (クェン酸、 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、 キレー卜剤、 水、 各種皮膚栄養剤、 生薬、 エキス、 精油等を必要 に応じて適宜配合することができる。  In addition to the above-mentioned components (A) and (B), the skin external preparation of the present invention may be a component usually used in skin external preparations such as pharmaceuticals, quasi-drugs, and cosmetics, for example, whitening agents, humectants, Inhibitors, UV absorbers, nonionic surfactants (polyoxyethylene hydrogenated castor oil, etc.), oily components (scoulane, olive oil, higher alcohols, higher fatty acids, etc.), thickeners (hydroxyethyl cellulose, xanthan gum, carboxy) Vinyl alcohols), alcohols (glycerin, 1,3-butylendalcol, ethanol, etc.), organic acids (cunic acid, succinic acid, adipic acid, lactic acid), pH adjusters (sodium hydroxide) , Potassium hydroxide, etc.), powder components, coloring agents, aqueous components, preservatives, antioxidants, fragrances, chelating agents, water, various skin nutrition agents, crude drugs, extracts, It may be blended in accordance with oil or the like as required.
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 —ム、 乳液、 ローション、 ジエル等の形態にすることができる。 実施例  The external preparation for skin of the present invention can be produced according to a usual method, and can be in the form of, for example, a cream, an emulsion, a lotion, a jewel, and the like. Example
実施例 1 Example 1
次の組成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。 02 09270 A skin external preparation having the following composition was prepared by a conventional method, and evaluated for percutaneous absorption, irritation, and feeling upon use. Table 1 shows the results. 02 09270
(組成) :セドロール 0 . 1 (重量%) (Composition): Cedrol 0.1 (% by weight)
界面活性剤 (表 1 )  Surfactants (Table 1)
モノステアリン酸ソノレビタン 1  Sonorebitan monostearate 1
グリセリン 5  Glycerin 5
オリープ油 1  Olive oil 1
1, 3—プ、チレングリコーノレ 5  1, 3-loops, polyethylene glycol 5
精製水  purified water
(評価方法)  (Evaluation method)
( 1 ) 経皮吸収性:  (1) Percutaneous absorption:
パネラー (1 0名) の上腕部に、 開孔径 1 6 ramの孔のあいたパッチテスト用バ ンソゥ膏を貼った後、 試料 2 0 0 Lを塗布した。 塗布後、 6時間でバンソゥ膏 をはがし、 次レ、で塗布部をセ口ハンテープで 1 0回テープストリップビングを行 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。  A patch test patch having a hole diameter of 16 ram was applied to the upper arm of the panelists (10 persons), and 200 L of the sample was applied. After the application, the banso plaster was peeled off for 6 hours, and in the next step, the application portion was tape-striped 10 times with a velcro tape to measure the amount of cedrol in the stratum corneum adhered to the cellophane tape.
セドロールの定量は、 1 0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一で測定した。 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。  The quantitative determination of cedrol was performed by gas chromatography using ethanol extract from 10 cellophane tapes. The percutaneous absorption rate was determined by the following formula, and was determined according to the criteria.
セロハンテープに密着した角層中のセドロール量 (10人の平均値) 経皮吸収率(%): X 100  Amount of cedrol in the stratum corneum in close contact with cellophane tape (average value of 10 persons) Percutaneous absorption (%): X 100
塗布したセドロール量 経皮吸収性判定基準: 1 ;経皮吸収率 1 %未満  Amount of cedrol applied Percutaneous absorption criteria: 1; Percutaneous absorption less than 1%
2 ;経皮吸収率 1 %以上 2 %未満  2; Percutaneous absorption rate 1% or more and less than 2%
3 ;経皮吸収率 2。/。以上 3 %未満  3; Percutaneous absorption 2. /. More than 3%
4 ;経皮吸収率 3 %以上  4; Percutaneous absorption rate 3% or more
( 2 ) 刺激性:  (2) Irritation:
敏感肌パネラー (1 0名) に、 石験で洗顔後、 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、 力ッコ内はセドロールを 配合しない場合の刺激性である。  After washing the face with a stone test, sensitive skin panelists (10 persons) were applied with each skin external preparation, and the state of the skin one minute later was determined according to the following criteria. In the results in Table 1, the irritability in the case of cedrol is not shown.
刺激性判定基準: A;少しでも刺激感を感じた人数 0名  Irritation criteria: A; Number of people who felt a little irritation 0 people
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 B: 1-2 people who felt a little irritation C: 3-5 people who felt a little irritation
D;少しでも刺激感を感じた人数 6〜 1 0名  D: Number of people who felt a little irritation 6-10
( 3 ) 使用感:  (3) Usability:
美容専門パネラー (1 0名) 、 各皮膚外用剤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。  Beauty panelists (10 people) evaluated the feeling of use when using each skin external preparation according to the following evaluation criteria, and the evaluation criteria were used.
評価基準: 1 ;ベたつかない  Evaluation criteria: 1; non-sticky
2 ;わずかにベたつく  2; slightly sticky
3 ;ベたつく  3; sticky
4 ;著しくベたつく  4; markedly sticky
使用感判定基準: A;平均評価点 1 . 5未満  Usability judgment criteria: A; average evaluation point less than 1.5
B ;平均評価点 1 . 5以上 2 5未満  B: Average score of 1.5 or more and less than 25
C;平均評価点 2 . 5以上 3 5未満  C: Average score 2.5 or more and less than 35
D;平均評価点 3 . 5以上  D: Average score of 3.5 or more
* :カツコ内はセドロールを酉己合しない場合。 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。  *: When Katsuko does not pick up cedrols. All of the products 1 to 4 of the present invention had improved percutaneous absorption, had no irritation, and were excellent in usability.
実施例 2 (乳液) セドロール 0. ポリオキシエチレン (4) ラウリルエーテルリン酸ナトリウム 0. 3 N—ステアロイルー N—メチルタゥリンナトリウム 1 モノステアリン酸ソルビタン 0. 3 ォリーブ油 2. 5 Example 2 (Emulsion) Cedrol 0. Polyoxyethylene (4) sodium lauryl ether phosphate 0.3 N-Stearoyl-N-methyltadulin sodium 1 Sorbitan monostearate 0.3 Olive oil 2.5
2. 5 コレステロール 0, 2 ィソステアリン酸コレステリル 0, 14 セチノレアノレコ^ "ノレ 0 3 ステアリルアルコール 0 2 グリセリン 10 カルボキシビ二ルポリマー  2.5 Cholesterol 0,2 Cholesteryl disostearate 0,14 Cetinorea noreco ^ "Nore 03 Stearyl alcohol 02 Glycerin 10 Carboxyvinyl polymer
(カーボポール 981、 B. F. GOODRICH社製) 0. 2 水酸化カリウム 0. 07 酸 0. 01 ユー力リエキス  (Carbopol 981, manufactured by BF GOODRICH) 0.2 Potassium hydroxide 0.07 Acid 0.01 Yurikuri extract
(ユーカリ抽出液 BG、 一丸フアルコス社製)  (Eucalyptus extract BG, manufactured by Ichimaru Fuarcos)
マ -ェエキス  Ma-e extract
(ファノレコレックス マロニエ B、 一丸フアルコス社製) 0. 5 ローズマリ一油 0. 1 パラォキシ安息香酸エステル 0. 2  (Fanorecorex Maronnier B, manufactured by Ichimaru Fuarcos) 0.5 Rosemari Mono Oil 0.1 Paraoxybenzoate 0.2
実施例 3 (ジエル) セドロール 0. 1 ポリオキシエチレン (10) セチルエーテルリン酸ナトリウム 0. 2 パルミ トイルサノレコシンナトリウム 0. 2 ポリオキシエチレン (40) 硬化ヒマシ油 0. 2 メチルポリシロキサン (50cs) 5 グリセリン 6Example 3 (Giel) Cedrol 0.1 Polyoxyethylene (10) Sodium Cetyl Ether Phosphate 0.2 Palmitoyl Sanolecosin Sodium 0.2 Polyoxyethylene (40) Hardened Castor Oil 0.2 Methyl Polysiloxane (50cs ) Five Glycerin 6
1, 3—プチレングリコーノレ 1,3-butylene glycolonole
カノレボキシビニノレポリマー  Canoleboxybininole polymer
(カーボポール 980、 B. F. GOODRICH社製) 0. 7 ァゼライン酸 0. 02 水酸化力リウム 0. 3 パラォキシ安息香酸エステル 0. 3 ローヤノレゼリ一エキス  (Carbopol 980, manufactured by BF GOODRICH) 0.7 Azelaic acid 0.02 Potassium hydroxide 0.3 Paraoxybenzoic acid ester 0.3 Royal anolyzeri extract
(ローヤルゼリーエキス、 一丸フアルコス社製) 0. 3 チヤエキス (緑茶リキッド、 —丸フアルコス社製) 0. 1 精製水  (Royal jelly extract, manufactured by Ichimaru Fuarcos) 0.3 Cya extract (green tea liquid, manufactured by Maru Fuarcos) 0.1 Purified water
実施例 4 (ローション) セドロール 0. 005 ラウロイルー βーァラニンナトリウム 0. 2 ォリーブ油 Example 4 (Lotion) Cedrol 0.005 Lauroylu Sodium β-alanine 0.2 Olive oil
メチルポリシロキサン (6cs) 2 ポリオキシエチレン (60) 硬化ヒマシ油 2 グリセリン 1 トリメチルダリシン 2 アクリル酸 . メタタリル酸アルキル共重合体  Methyl polysiloxane (6cs) 2 Polyoxyethylene (60) Hardened castor oil 2 Glycerin 1 Trimethyldaricin 2 Acrylic acid. Alkyl methacrylate copolymer
(PEMULEN TR— 1、 B. F. GOODRICH社製) 0. 3 水酸化カリウム 0. 2  (PEMULEN TR-1, manufactured by BF GOODRICH) 0.3 Potassium hydroxide 0.2
0. 06 ェデト酸 2ナトリゥム 0. 02 パラォキシ安息香酸ェステル 0. 5 アロエエキス  0.06 Edetic acid 2-sodium 0.02 Paroxybenzoic acid ester 0.5 Aloe extract
(ファノレコレックス アロエ KB、 一丸フアルコス社製) 0. 5 ユー力リ油 0. 0 精製水 (Fanorecorex Aloe KB, manufactured by Ichimaru Fuarcos) 0.5 Yurikuri Oil 0.0 purified water
実施例 5 (クリーム) セド、口一ノレ 0 . 5 ポリオキシエチレン (8 ) ォレイルエーテルリン酸ナトリウム 0 . 2 ステアリン酸ポリグリセリルー 5 3 5 パルミ トイルサルコシンナトリウム 0 2 セチノレアノレコーノレ 1 5 ステアリルアルコール 1 Example 5 (Cream) Sed, Mouth 0.5 Polyoxyethylene (8) Sodium Oleyl Ether Phosphate 0.2 Polyglyceryl Stearate 5 35 5 Sodium Palmitoyl Sarcosine 0 2 Cetinoleanorecoronole 15 15 Stearyl Alcohol 1
N - ( 3—へキサデシロキシー2—ヒドロキシプロピル) 一 Ν ·  N-(3-hexadecyloxy-2-hydroxypropyl) 1 Ν ·
2—ヒド口キシェチルへキサデ力ナミ ド 4 コレステロ一ノレ 0 . 8 ィソステアリン酸コレステリル 0 . 5 ォリーブ油 2 . 7 メチルポリシロキサン (50cs) 4 グリセリン 2 0 コ/ヽク酸 0 0 2 水酸化ナトリウム 0 0 0 2 パラォキシ安息香酸: 0 2 スギナエキス 0 2 2-Hydrox-kisethyl hexademamide 4 Cholesterol 0.8 0.8 Cholesteryl disostearate 0.5 Olive oil 2.7 Methylpolysiloxane (50cs) 4 Glycerin 20 Co / oxalic acid 0 0 2 Sodium hydroxide 0 0 0 2 Paraoxybenzoic acid: 0 2 Horsetail extract 0 2
(スギナ抽出液 BG、 丸善製薬社製) 0 2 ハマメ リスエキス (Brown horse extract BG, manufactured by Maruzen Pharmaceutical Co., Ltd.) 0 2 Hamamelis extract
(ファノレコレックス ハマメ リス B、 一丸フアルコス社製) 0 . 1 水  (Fanorecorex Hamamelis B, manufactured by Ichimaru Fuarcos) 0.1 Water
実施例 2〜 5の皮膚外用剤は、 レ、ずれもセドロ一ルの経皮吸収性に優れ、 抗炎 症作用、 抗アレルギー (I L 4産生抑制) 作用、 刺激緩和作用に優れ、 使用感も 良好である。 産業上の利用可能十生 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、 抗ァ レルギ一 (I L4産生抑制) 作用、 刺激緩和作用に優れ、 使用感も良好である。 The skin external preparations of Examples 2 to 5 are excellent in percutaneous absorbability of cedrol, and are excellent in anti-inflammatory, anti-allergic (suppressing IL-4 production), stimulating alleviation, and feeling of use. Good. Industrial availability The external preparation for skin of the present invention improves the transdermal absorbability of cedrol, is excellent in anti-inflammatory action, anti-allergic (IL4 production inhibition) action, irritation relieving action, and has good feeling in use.

Claims

請求の範囲 The scope of the claims
1. 次の成分 (A) 及び (B) : 1. The following components (A) and (B):
(A) セドロール、  (A) Cedrol,
(B) ァニオン界面活性剤  (B) Anionic surfactant
を含有する皮膚外用剤。 An external preparation for skin containing.
2. 成分 (B) 、 リン酸エステル基を有するァニオン界面活性剤である請求項 1記載の皮膚外用剤。  2. The external preparation for skin according to claim 1, wherein the component (B) is an anionic surfactant having a phosphate group.
3. 成分 (B) が、 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、 及びモノ又はジ (ポリオキシエチレン (2〜20) C6〜C24アルキル又 はァルケ二ル) リン酸エステル塩から選ばれるものである請求項 2記載の皮膚外 用剤。 3. Component (B) is a mono- or di- (C 6 -C 24 ) alkyl or alkenyl phosphate ester salt, and a mono- or di- (polyoxyethylene (2-20) C 6 -C 24 alkyl or alkenyl 3. The external preparation for skin according to claim 2, which is selected from phosphoric acid ester salts.
4. 成分 (B) 力 炭素数 14以上のァシル基を持つァシルアミノ基を有するァ 二オン界面活性剤である請求項 1記載の皮膚外用剤。  4. The external preparation for skin according to claim 1, which is an anionic surfactant having an acylamino group having an acyl group having 14 or more carbon atoms as the component (B).
5. 成分 (B) が、 N— C14〜C24ァシルサルコシン塩、 N_C14〜C24ァシルメチ ルタゥリン塩、 N— C14〜C24ァシルグルタミン酸塩、 N— C14〜C24ァシルアルギ ニン塩、及び N— C14〜C24ァシルメチルァラニン塩から選ばれるものである請求 項 4記載の皮膚外用剤。 5. Component (B) is, N- C 14 ~C 24 Ashirusarukoshin salts, N_C 14 -C 24 Ashirumechi Ruturin salts, N- C 14 ~C 24 § sill glutamate, N- C 14 ~C 24 Ashiruarugi Nin salts, and N-C 14 -C 24 skin external preparation according to claim 4, wherein those selected from § sill methyl § La Nin salt.
6. 成分(A) を 0. 001〜 10重量%、成分(B) を 0. 001〜10重量% 含有する請求項 1〜 5のいずれか 1項記載の皮膚外用剤。  6. The external preparation for skin according to any one of claims 1 to 5, comprising 0.001 to 10% by weight of the component (A) and 0.001 to 10% by weight of the component (B).
PCT/JP2002/009270 2001-09-11 2002-09-11 External preparations for the skin WO2003022257A1 (en)

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EP3384905A1 (en) * 2017-04-05 2018-10-10 University Of Seoul Industry Cooperation Foundation Composition for preventing or ameliorating hypersensitive skin comprising cedrol or derivatives thereof, or pharmaceutically acceptable salts thereof
CN108685883A (en) * 2017-04-05 2018-10-23 首尔市立大学校产学协力团 Including the pharmaceutical composition for preventing or treating autoimmune disease of cedar wood alcohol or derivatives thereof or its pharmaceutically acceptable salt
CN108685881A (en) * 2017-04-05 2018-10-23 首尔市立大学校产学协力团 Including the cosmetic composition for preventing or improving allergic skin of cedar wood alcohol or derivatives thereof or its pharmaceutically acceptable salt
US10307383B2 (en) 2017-04-05 2019-06-04 University Of Seoul Industry Cooperation Foundation Cosmetic composition for preventing or ameliorating hypersensitive skin comprising cedrol or derivatives thereof, or pharmaceutically acceptable salts thereof
CN108685883B (en) * 2017-04-05 2021-07-09 首尔市立大学校产学协力团 Pharmaceutical composition for preventing or treating autoimmune diseases comprising cedrol or a derivative thereof or a pharmaceutically acceptable salt thereof

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