TW200922631A - Vesicle composition and external preparation for skin - Google Patents

Vesicle composition and external preparation for skin Download PDF

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Publication number
TW200922631A
TW200922631A TW097127163A TW97127163A TW200922631A TW 200922631 A TW200922631 A TW 200922631A TW 097127163 A TW097127163 A TW 097127163A TW 97127163 A TW97127163 A TW 97127163A TW 200922631 A TW200922631 A TW 200922631A
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TW
Taiwan
Prior art keywords
component
vesicle composition
vesicle
external preparation
skin
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Application number
TW097127163A
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Chinese (zh)
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TWI430813B (en
Inventor
Yoshikazu Konno
Original Assignee
Kose Corp
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Publication of TW200922631A publication Critical patent/TW200922631A/en
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Publication of TWI430813B publication Critical patent/TWI430813B/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/127Liposomes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14Liposomes; Vesicles
    • 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
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/361Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
    • 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
    • A61K8/55Phosphorus compounds
    • A61K8/553Phospholipids, e.g. lecithin
    • 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
    • A61K8/63Steroids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/16Emollients or protectives, e.g. against radiation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Toxicology (AREA)
  • Emergency Medicine (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)

Abstract

Disclosed is a vesicle composition containing (a) a lysophospholipid, (b) one or more substances selected from higher alcohols which are in a liquid state at 25 DEG C and liquid higher fatty acids, (c) cholesterol or phytosterol and (d) purified water.

Description

200922631 九、發明說明 【發明所屬之技術領域】 本發明係關於利用溶血磷脂質之囊泡組成物、及由該 囊泡分散組成物所形成之皮膚外用劑。 【先前技術】 囊泡係具有形成兩性物質之二分子膜結構之封閉小胞 ,因此特異的結構,可內包有效成分,作爲於藥物輸送系 統(Drug Deliver System)等之攜帶者而受到矚目。另外 ,囊泡於角質層中之滯留性高,使有效成分有效率地作用 ,所以係非常有效地作爲皮膚外用劑者。 一般存在許多可構成囊泡之兩性物質,尤其由磷脂質 所形成之囊泡稱爲微脂體(Liposome ),對生物體之安全 性面上亦進行許多檢討。例如鱗脂膽驗(P h 〇 s p h a t i d y 1 Choline)純度爲90%以上,由碘價爲0.1以下之磷脂質所 構成,粒徑爲1〇〇〜150nm之微脂體(例如參考專利文獻 1)等。另外,作爲構成囊泡之兩性物質’關於使用合成 界面活性劑之囊泡之檢討’進行許多的檢討。使用麥芽糖 醇二脂肪酸酯之囊泡製劑之技術(例如參考專利文獻2 ) 或使用多鏈多親水基型界面活性劑之微脂體之技術(例如 參考專利文獻3 )等。 另一方面,溶血磷脂質係親水性界面活性劑,使用作 爲水中油型乳化組成物之乳化劑之技術。例如以特定的比 率配合溶血鱗脂質及磷脂質及油之透明度高之化粧料(例 -4- 200922631 如參考專利文獻4)。另外,揭示含有磷脂質及規定的陽 離子界面活性劑之毛髮用化粧料,可使用溶血體作磷脂質 (參考專利文獻5)。 另外,液狀之高級醇或液狀之高級脂肪酸係使用作爲 使乳化粒子更微細化等之助乳化劑之技術(例如參考專利 文獻6 )。 另外,化粧料等之皮膚外用劑係作爲賦予各種美容效 果或附加價値之目的而配合電解質。例如胺基酸、d 1 -吡 咯烷酮羧酸鈉、乳酸鈉或作爲美白成分之抗壞血酸衍生物 等之有機鹽、或氯化鈉等之無機鹽等。 [專利文獻1]特開2006- 1 24378號公報 [專利文獻2]特開平06-157296號公報 [專利文獻3]特開2006-290894號公報 [專利文獻4]特開2001-302433號公報 [專利文獻5]特開2006-193461號公報 i [專利文獻6]特開2004-27734 1號公報 【發明內容】 [發明之揭示] [發明所欲解決之課題] 關h如此囊泡製劑之技術雖有許多,但仍有如下之問 題點。例如專利文獻i之技術,雖然使用感優異,但經時 變臭,或受限於安定製劑之pH範圍,應用於化粧料等之 皮膚外用劑爻到限制。專利文獻2之技術,與微脂體相比 -5- 200922631 較,對肌膚的滲透感低,感到發黏。另外,專利文獻3之 技術係利用胺基酸系界面活性劑,雖可以簡便的方法得到 囊泡,但關於其保存安定性並不充份。另外,於賦予保濕 效果或美白效果等目的等所配合之電解質存在下,實際情 況係如此技術破壞囊泡特有的二分子膜結構,於高溫之保 存性不足。 因此要求開發與上述技術相異之如微脂體般使用感優 異,而且形成保存安定性優異之囊泡之皮膚外用劑,進而 要求開發即使於電解質存在下,仍可形成囊泡之保存安定 性優異之皮膚外用劑。 [課題之解決手段] 於相關實際情況下,本發明者努力硏究的結果,發現 含有溶血磷脂質、1種或2種以上選自於25 t爲液狀之高 級醇或液狀之高級脂肪酸、膽固醇或植物甾醇、及精製水 之囊泡係具有優異的保存安定性,完成本發明。 本發明係提供使含有通常作爲親水性乳化劑所使用之 溶血磷脂質、1種或2種以上選自於25 °C爲液狀之高級醇 或液狀之高級脂肪酸、膽固醇或植物留醇、及精製水,新 穎且保存安定性優異之囊泡組成物者。 亦即,本發明係關於含有下述成分(a )〜(d ); (a )溶血磷脂質 (b ) 1種或2種以上選自於25t爲液狀之高級醇或 液狀之高級脂肪酸 -6- 200922631 (C )膽固醇或植物甾醇 (d )精製水 之囊泡組成物。 本發明亦關於更含有成分(e)電解質之上述囊泡組 成物。 另外,本發明亦關於成分(b)及成分(c)之含有質 量比(b ) / ( c )爲〇 . 2〜4之上述囊泡組成物。 另外’本發明亦關於成分(a)、成分(b)及成分( c)之含有質量比(a) /[(b) + (c)]爲0.25〜5之上述 囊泡組成物。 另外’本發明亦關於成分(b )係1種或2種以上選 自油醇、異硬脂醇、油酸、異硬脂酸之上述囊泡組成物。 另外,本發明亦關於於25 °C時之導電度爲0.02〜 2.5 s/m爲特徵之上述囊泡組成物。 另外,就其他觀點,依據本發明,提供含有上述任一 種之囊泡組成物之皮膚外用劑。 [發明之功效] 本發明之囊泡組成物係保存安定性優異。另外,對肌 膚的滲透感高,不發黏的使用感,進而具有保濕效果優異 之品質者,本發明之囊泡組成物係有效地作爲皮膚外用劑 [用以實施發明之最佳形態] 200922631 以下係詳細地說明本發明。另外,本說明書中使用「 〜」所表示之數値範圍係指包含「〜」前後所記載之數値 爲下限値及上限値之範圍。 本發明之囊泡組成物係含有(a )溶血磷脂質。(a ) 溶血磷脂質係使用爲囊泡組成物結構成分。關於該種類並 無特別限制。溶血磷脂質之例,包含來自大豆之溶血磷脂 質、來自大豆之氫化溶血磷脂質、來自蛋黃溶血磷脂質、 來自蛋黃之氫化溶血磷脂質等。此等溶血磷脂質係因應需 要,可使用一種、或二種以上。(a )溶血磷脂質係1種 酵素改性磷脂質,2位之酯鍵由磷脂酶所水解者。本發明 使用之溶血磷脂質係以溶血磷脂質之溶血化率(全磷脂質 中之溶血磷脂質之比率)爲60%以上,且磷脂膽鹼之純度 (以下爲「P C純度」)爲2 0 %以上者爲宜。因爲溶血磷 脂質之脂肪酸鏈爲1條,與脂肪酸鏈爲2條之磷脂質相比 較,親水性高,及具有與磷脂質相異的化學性質。 成分(a )溶血磷脂質之含量雖無特別限定,但以 0.01〜5質量% (以下單位簡略爲「%」)爲宜,以0.05〜 3 %尤佳。於此範圍時,可得到保存安定性更優異之囊泡組 成物。 另外,亦可同時倂用溶血磷脂質及磷脂質。 本發明之囊泡組成物係含有(b )於25 °C爲液狀之高 級醇或液狀之高級脂肪酸。成分(b )係必須爲囊泡結構 成分,含有此係可抑制成分(c )之結晶析出,可提升保 存安定性。另外,含有成分(b )而可得到對肌膚之滲透 -8- 200922631 感或不發黏之使用感,成爲尤其有效地作爲皮膚外用劑之 囊泡組成物。於25 °C爲液狀之高級醇之例,包括辛基十二 烷醇、油醇、異硬脂醇、異鯨蠟醇、椰子醇、橄欖醇、荷 荷芭醇、及癸基十四烷醇;於2 5 °C爲液狀之高級脂肪酸之 例,包括異硬脂酸、油酸、及亞油酸。可使用此等中之一 種或二種以上。其中以油醇、異硬脂醇、油酸、及異硬脂 酸爲宜。 成分(b )之含量雖非特別限定者,但以〇 . 0 1〜5 %爲 宜,以 0.0 5〜3 %尤佳。若於此範圍時,可得到保存安定 性優異之囊泡組成物。 本發明之囊泡組成物係含有(c )膽固醇或植物甾醇 。(c )膽固醇或植物甾醇係幫助形成囊泡時二分子膜結 構之安定性,含有此而可提升保存安定性。 成分(c )之含量雖非特別限定者,但以〇 . 0 1〜5 %爲 宜,以 0.0 5〜3 %尤佳。若於此範圍時,可得到保存安定 性優異之囊泡組成物。 本發明之囊泡組成物中,成分(b)與成分(c)之含 有質量比(b) / (c)若於0.2〜4之範圍時,囊泡之保存 安定性將爲更加良好者,若於0.5〜2時,保存安定性將 爲進一步更加良好者。另外,本發明之囊泡組成物中,成 分(a)、成分(b)與成分(c)之含有質量比(a) /[(b )+ ( c )]若於0.25〜5之範圍時,囊泡之保存安定性將 爲更加良好者,若於〇 . 4〜4之範圍時,保存安定性將爲 進一步更加良好者。 -9- 200922631 本發明之囊泡組成物係含有(d)精製水》(d)精製 水係作爲成分(a )〜(c )之分散介質者,係作爲含有囊 泡之皮膚外用劑之必須成分。該具體之配合量係可依成分 (a)〜(c)之含量所適當決定,大約50〜99 %。 本發明之囊泡組成物係藉由親水性之成分(a )、及 親油性之成分(b )及成分(c )之親水性一親油性之平衡 ’於成分(d)中成爲二分子膜結構。成分(a)之溶血磷 脂質係如所述,因爲與通常之磷脂質比較,親水性高,所 以不利於形成囊泡。本發明中,藉由使用成分(a )溶血 磷脂質、成分(b )液狀之高級醇或液狀之高級脂肪酸、 及成分(c )之膽固醇或植物甾醇,補充此點,取得親水 性-親油性之平衡,提供安定的囊泡組成物。 本發明之囊泡組成物係可作爲皮膚外用劑使用。此形 態係以更含有成分(e )電解質爲宜。(e )電解質係配合 以賦予保濕效果、消炎效果或美白效果等之目的者。 具有保濕效果之電解質例,包含尿素、或胺基酸、乳 酸、檸檬酸、吡咯烷酮羧酸等之有機化合物、及此等之鉀 、鈉、鎂、鈣等之金屬鹽、氯化鈉、氯化鎂等之無機鹽。 另外,具有消炎功效之電解質例’包含甘草酸、泛酸 等之有機化合物、此等鉀、鈉、鎂、鈣等之金屬鹽等。 另外,具有美白功效之電解質例’包含抗壞血酸磷酸 酯、抗壞血酸烷基酯、抗壞血酸硫酸酯 '抗壞血酸葡萄苷 等、及此等之鈉、鉀、鎂、鈣等之金屬鹽等之抗壞血酸類 -10- 200922631 另外,亦可舉例如海洋深層水、溫泉水等、含有此等 電解質等之來自天然的水溶液。此等係可組合一種或二種 以上使用。 此等中,作爲皮膚外用劑所使用之形態,(e )電解 質係以具有美白效果之水溶性抗壞血酸衍生物、具有保濕 效果之乳酸鹽、吡咯烷酮羧酸鹽等爲適合例。 另外,上述皮膚外用劑所使用之電解質之具體例係記 載於中西紀元及其他「Fragrance Journal」社1995-1 P.71 〜8 0 ;及「化粧品之有效性」藥事日報社p. 1 5 0。 成分(e)之含量雖非特別限定者,但以〇.〇1〜10 %爲 宜,以〇· 1〜5%尤佳。若於此範圍時,不損及保存安定性 ,可得到有效地作爲保濕效果、消炎效果、或美白效果優 異之皮膚外用劑之囊泡組成物。添加電解質通常會使囊泡 不安定化,但因爲本發明之囊泡組成物之安定性高,所以 作爲保濕效果、消炎效果、或美白效果等之藥效成分,即 使添加電解質,仍維持良好的安定性。 本發明之囊泡組成物係除了上述必須成分(a )〜(d )以外,亦可含有各種成分。尤其含有多元醇,可得到保 存安定性或使用感等更優異之囊泡組成物。作爲如此多元 醇,雖無特別限制,但於該例中包含丙二醇、1,3 - 丁二醇 、二丙二醇、1,2 -戊二醇、甘油、二甘油、山梨糖醇等。 其中以1,3-丁二醇、二丙二醇尤佳。 本發明之囊泡組成物於2 5 °C時之導電度(使用東亞電 波工業社製導電度計CM-60G測定)係以〇.〇2〜2.5s/m爲 -11 - 200922631 宜。以0_ 05〜2 s/m尤佳。若於此範圍時’不損及囊泡之 保存安定性,可充份地發揮(e )電解質之效果’例如保 濕效果、消炎效果、或美白效果。 本發明之囊泡組成物係可依各種方法製造。該一例係 以溫度8 0 °C程度,使成分(a )及成分(c )溶解於成分( b )之溶液,以及攪拌混合於溫度爲80°C程度之成分(d ) (因應所需,加熱成分(e ),使溶解)後,緩緩冷卻至 室溫之方法。 本發明亦關於本發明之含有囊泡組成物之皮膚外用劑 。本發明之皮膚外用劑係於不妨礙本發明功效之範圍,可 添加通常的皮膚外用劑所配合之任意成分,具體上如成分 (b )以外之油劑、醇類、粉體、水溶性高分子、被膜形 成劑、界面活性劑、油溶性膠化劑、有機改性黏土礦物、 樹脂、紫外線吸收劑、防腐劑、抗菌劑、香料、抗氧化劑 、pH調整劑、螯合劑等。 本發明之皮膚外用劑之用途係可舉例如化粧水、乳液 、乳霜 '美容液、按摩料、面膜料、護手霜、身體乳霜等 之護膚化粧料、化粧用打底化粧料。另外,該使用法係可 舉例如以手或手指使用之方法 '使不織布含浸而使用之方 法等。 【實施方式】 [實施例] 以下係舉實施例更詳細地說明本發明,但本發明並非 -12- 200922631 局限於此等者。 [實施例1] 本發明品1〜1 7及比較品1〜5 依據下述製法,調製表1〜表 物。確認囊泡形成係於偏光顯微鏡 十字(M a 11 e s e C r 〇 s s )像的量判斷 另外,以此等囊泡組成物作爲 進行評估該使用感及保濕效果。更 對於(1 )滲透感、(2 )有無發黏 進行官能評估。合倂結果如表1〜赛 :美容液 4所示組成之囊泡組成 觀察下進行,由馬耳他 〇 美容液,塗佈於皮膚, 具體上’由專業調查員 、及(3 )保濕效果, ^ 4所示。 -13- 200922631 [表i]BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a vesicle composition using a lysophospholipid and an external preparation for skin formed from the vesicle-dispersed composition. [Prior Art] The vesicle has a closed cell which forms a dimeric membrane structure of an amphoteric substance, and therefore a specific structure, which can contain an active ingredient, is attracting attention as a carrier of a drug delivery system (Drug Deliver System). Further, since the vesicle has high retention in the stratum corneum and the active ingredient acts efficiently, it is very effective as a skin external preparation. There are many amphoteric substances that can form vesicles. In particular, vesicles formed by phospholipids are called liposome, and many reviews have been made on the safety aspects of organisms. For example, Ph 〇sphatidy 1 Choline has a purity of 90% or more, and is composed of a phospholipid having an iodine value of 0.1 or less, and a liposome having a particle diameter of 1 to 150 nm (for example, refer to Patent Document 1). Wait. In addition, many reviews have been conducted as a review of the vesicles' amphiphilic substance 'reports on vesicles using synthetic surfactants'. A technique of using a vesicle preparation of maltitol difatty acid ester (for example, refer to Patent Document 2) or a technique of using a liposome of a multi-chain polyhydric-based surfactant (for example, refer to Patent Document 3). On the other hand, a lysophospholipid-based hydrophilic surfactant is a technique using an emulsifier as an oil-based emulsified composition. For example, a cosmetic having a high transparency of a lytic squamous lipid and a phospholipid and an oil is blended at a specific ratio (Example -4-200922631, see Patent Document 4). Further, a cosmetic for hair containing a phospholipid and a predetermined cationic surfactant can be used, and a lysosome can be used as a phospholipid (refer to Patent Document 5). Further, a liquid higher alcohol or a liquid higher fatty acid is used as a co-emulsifier such as a finer emulsified particle (for example, refer to Patent Document 6). Further, an external preparation for skin such as a cosmetic is blended with an electrolyte for the purpose of imparting various cosmetic effects or an additional price. For example, an amino acid, an organic salt such as sodium d 1 -pyrrolidonecarboxylate, sodium lactate or an ascorbic acid derivative as a whitening component, or an inorganic salt such as sodium chloride. [Patent Document 1] Japanese Laid-Open Patent Publication No. JP-A No. Hei. No. 2006-302. [Patent Document 5] JP-A-2006-193461 (Patent Document 6) JP-A-2004-27734 No. 2004-A SUMMARY OF THE INVENTION [Disclosure of the Invention] [Problems to be Solved by the Invention] Technology for such a vesicle preparation Although there are many, there are still the following problems. For example, the technique of Patent Document i is excellent in the feeling of use, but it is odor-prone over time, or is limited by the pH range of the customizing agent, and is limited to a skin external preparation for use in cosmetics and the like. The technique of Patent Document 2 is compared with the liposome -5-200922631, and has a low penetration into the skin and feels sticky. Further, the technique of Patent Document 3 utilizes an amino acid-based surfactant, and although a vesicle can be obtained by a simple method, it is not sufficient for its storage stability. Further, in the presence of an electrolyte to which a moisturizing effect, a whitening effect, or the like is imparted, the actual situation is such that the technique destroys the specific molecular structure of the vesicle and is insufficient in storage at high temperatures. Therefore, it is required to develop an external preparation for skin which is excellent in the use of a liposome, which is different from the above-mentioned technique, and which forms a vesicle excellent in preservation stability, and further requires development of a storage stability of a vesicle even in the presence of an electrolyte. Excellent skin external preparation. [Means for Solving the Problem] In the actual situation, the inventors of the present invention have found that lysophospholipids, one or two or more kinds of higher alcohols selected from liquid alcohols or liquid higher fatty acids The vesicles of cholesterol, phytosterol, and purified water have excellent preservation stability, and the present invention has been completed. The present invention provides a lysophospholipid which is usually used as a hydrophilic emulsifier, one or two or more kinds of higher alcohols, liquid or higher fatty acids, cholesterol or phytosterols selected from liquids at 25 ° C, And refined water, novel and preserved vesicle composition with excellent stability. That is, the present invention relates to the following components (a) to (d); (a) lysophospholipid (b) one or more selected from the group consisting of 25t liquid high alcohol or liquid higher fatty acid -6- 200922631 (C) Cholesterol or phytosterol (d) vesicle composition of purified water. The present invention also relates to the above vesicle composition further comprising the component (e) electrolyte. Further, the present invention relates to the above-mentioned vesicle composition of the component (b) and the component (c) in which the mass ratio (b) / (c) is 〇. 2 to 4. Further, the present invention relates to the above-mentioned vesicle composition having a mass ratio (a) / [(b) + (c)] of the component (a), the component (b) and the component (c) of 0.25 to 5. Further, the present invention relates to the component (b) which is one or more selected from the group consisting of oleyl alcohol, isostearyl alcohol, oleic acid and isostearic acid. Further, the present invention relates to the above vesicle composition characterized by having a conductivity of 0.02 to 2.5 s/m at 25 °C. Further, from another viewpoint, according to the present invention, a skin external preparation containing the vesicle composition of any of the above is provided. [Effect of the Invention] The vesicle composition of the present invention is excellent in storage stability. In addition, the vesicle composition of the present invention is effective as an external preparation for skin [the best form for carrying out the invention] when the sensation of penetration to the skin is high, the feeling of use is not sticky, and the hydration effect is excellent. The invention is described in detail below. In addition, the numerical range indicated by "~" in this specification means the range which contains the number 値 before and after "~" as the lower limit 値 and upper limit 値. The vesicle composition of the present invention contains (a) a lysophospholipid. (a) The lysophospholipid system is used as a structural component of the vesicle composition. There is no particular limitation on this type. Examples of the lysophospholipids include lysophospholipids derived from soybeans, hydrogenated lysophospholipids derived from soybeans, hydrolyzed phospholipids derived from egg yolk, hydrogenated lysophospholipids derived from egg yolk, and the like. These lysophospholipids may be used alone or in combination of two or more. (a) The lysophospholipid is an enzyme-modified phospholipid, and the ester bond at the 2-position is hydrolyzed by a phospholipase. The lysophospholipid used in the present invention has a hemolytic rate of lysophospholipid (the ratio of lysophospholipid in whole phospholipids) of 60% or more, and the purity of phospholipid choline (hereinafter referred to as "PC purity") is 20. More than % is appropriate. Since the lysophosphorus lipid has one fatty acid chain, it has higher hydrophilicity and chemical properties different from those of phospholipids, compared with two phospholipids having a fatty acid chain. The content of the component (a) lysophospholipid is not particularly limited, but is preferably 0.01 to 5% by mass (hereinafter, the unit is simply "%"), and more preferably 0.05 to 3%. In this range, a vesicle composition which is more excellent in preservation stability can be obtained. In addition, lysophospholipids and phospholipids can also be used at the same time. The vesicle composition of the present invention contains (b) a higher alcohol or a liquid higher fatty acid which is liquid at 25 °C. The component (b) must be a vesicle structure component, and the system can suppress the precipitation of crystals of the component (c), thereby improving the preservation stability. In addition, the component (b) contains a feeling of infiltration into the skin -8-200922631, and it is a vesicle composition which is particularly effective as a skin external preparation. Examples of higher alcohols which are liquid at 25 ° C, including octyldodecanol, oleyl alcohol, isostearyl alcohol, isoctanol, coconut alcohol, olive alcohol, jojobaol, and mercapto fourteen An alkanol; an example of a higher fatty acid in liquid form at 25 ° C, including isostearic acid, oleic acid, and linoleic acid. One or more of these may be used. Among them, oleyl alcohol, isostearyl alcohol, oleic acid, and isostearic acid are preferred. The content of the component (b) is not particularly limited, but is preferably 〇1 to 5%, preferably 0.05 to 3%. When it is in this range, a vesicle composition excellent in preservation stability can be obtained. The vesicle composition of the present invention contains (c) cholesterol or phytosterol. (c) Cholesterol or phytosterols contribute to the stability of the bimolecular membrane structure when vesicles are formed, and this enhances preservation stability. The content of the component (c) is not particularly limited, but is preferably 〇1 to 5%, and particularly preferably 0.05 to 3%. When it is in this range, a vesicle composition excellent in preservation stability can be obtained. In the vesicle composition of the present invention, when the mass ratio (b) / (c) of the component (b) to the component (c) is in the range of 0.2 to 4, the storage stability of the vesicles is further improved. If it is 0.5 to 2, the preservation stability will be further better. Further, in the vesicle composition of the present invention, the mass ratio (a) / [(b ) + ( c )] of the component (a), the component (b) and the component (c) is in the range of 0.25 to 5 The preservation stability of the vesicles will be even better. If it is in the range of 4 to 4, the preservation stability will be further better. -9- 200922631 The vesicle composition of the present invention contains (d) purified water (d) purified water as a dispersion medium of components (a) to (c), which is required as a skin external preparation containing vesicles. ingredient. The specific compounding amount can be appropriately determined depending on the contents of the components (a) to (c), and is about 50 to 99%. The vesicle composition of the present invention is a bimolecular film in the component (d) by the hydrophilic component (a), the lipophilic component (b), and the hydrophilic-lipophilic balance of the component (c). structure. The hemolytic phosphorus lipid of the component (a) is as described above, and since it has high hydrophilicity as compared with the usual phospholipids, it is disadvantageous for the formation of vesicles. In the present invention, by using the component (a) lysophospholipid, the component (b) liquid higher alcohol or the liquid higher fatty acid, and the component (c) cholesterol or phytosterol, this is supplemented to obtain hydrophilicity - A balance of lipophilicity provides a stable vesicle composition. The vesicle composition of the present invention can be used as an external preparation for skin. This form is preferably more containing the component (e) electrolyte. (e) The electrolyte is blended to impart a moisturizing effect, an anti-inflammatory effect, a whitening effect, and the like. Examples of the electrolyte having a moisturizing effect include organic compounds such as urea, or amino acid, lactic acid, citric acid, and pyrrolidone carboxylic acid, and metal salts such as potassium, sodium, magnesium, and calcium, sodium chloride, magnesium chloride, and the like. Inorganic salt. Further, the electrolyte example having an anti-inflammatory effect includes an organic compound such as glycyrrhizic acid or pantothenic acid, or a metal salt such as potassium, sodium, magnesium or calcium. Further, an electrolyte example having a whitening effect includes ascorbic acid phosphate such as ascorbyl phosphate, ascorbyl alkyl ester, ascorbyl sulfate, ascorbyl glucoside, or the like, and a metal salt such as sodium, potassium, magnesium or calcium. 200922631 Further, for example, deep water of the ocean, hot spring water, or the like, a natural aqueous solution containing such an electrolyte or the like may be mentioned. These may be used alone or in combination of two or more. In the form of the skin external preparation, (e) the electrolytic substance is a water-soluble ascorbic acid derivative having a whitening effect, a lactate having a moisturizing effect, a pyrrolidone carboxylate or the like, and the like. Further, specific examples of the electrolyte used for the external preparation for skin are described in the Western and Western Ages and other "Fragrance Journal" 1995-1 P.71 to 80; and "The Effectiveness of Cosmetics" Pharmaceutical Daily News p. 1 5 0. The content of the component (e) is not particularly limited, but it is preferably from 1 to 10%, particularly preferably from 1 to 5%. When it is in this range, the vesicle composition which is effective as a skin external preparation which is effective as a moisturizing effect, an anti-inflammatory effect, or a whitening effect can be obtained without impairing the preservation stability. The addition of the electrolyte usually causes the vesicles to be unstable, but since the vesicle composition of the present invention has high stability, it is maintained as a medicinal component such as a moisturizing effect, an anti-inflammatory effect, or a whitening effect, even if an electrolyte is added. Stability. The vesicle composition of the present invention may contain various components in addition to the above-mentioned essential components (a) to (d). In particular, when a polyhydric alcohol is contained, a vesicle composition which is more excellent in stability and use feeling can be obtained. The polyol is not particularly limited, but in this example, propylene glycol, 1,3-butanediol, dipropylene glycol, 1,2-pentanediol, glycerin, diglycerin, sorbitol or the like is contained. Among them, 1,3-butanediol and dipropylene glycol are particularly preferred. The conductivity of the vesicle composition of the present invention at 25 ° C (measured using a conductivity meter CM-60G manufactured by Toa Denpa Kogyo Co., Ltd.) is preferably 〜 2 2.5 2.5 s / m s -11 - 200922631. It is especially good at 0_ 05~2 s/m. If it is in this range, the effect of the electrolyte (e), such as a moisturizing effect, an anti-inflammatory effect, or a whitening effect, can be sufficiently exhibited without impairing the storage stability of the vesicles. The vesicle composition of the present invention can be produced by various methods. This example is a solution in which the component (a) and the component (c) are dissolved in the component (b) at a temperature of 80 ° C, and the component (d) is stirred and mixed at a temperature of 80 ° C (according to the need, After heating the component (e) to dissolve it, it is slowly cooled to room temperature. The present invention also relates to a skin external preparation containing a vesicle composition of the present invention. The external preparation for skin of the present invention may be added to a conventional skin external preparation in an amount which does not impair the efficacy of the present invention, and specifically, an oil agent, an alcohol, a powder, and a water-soluble substance other than the component (b). Molecules, film forming agents, surfactants, oil-soluble gelling agents, organically modified clay minerals, resins, ultraviolet absorbers, preservatives, antibacterial agents, perfumes, antioxidants, pH adjusters, chelating agents, and the like. The use of the external preparation for skin of the present invention may, for example, be a lotion, a lotion, a cream, a beauty lotion, a massage lotion, a facial mask, a hand cream, a body cream, or the like, and a cosmetic base. Further, the method of use can be exemplified by a method of using a hand or a finger, a method of impregnating a nonwoven fabric, or the like. [Embodiment] [Examples] Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to -12-200922631. [Example 1] Inventive products 1 to 17 and comparative products 1 to 5 were prepared in accordance with the following production methods. It was confirmed that the vesicle formation was determined by the amount of the polarizing microscope cross (M a 11 e s e C r 〇 s s ) image. Further, the vesicle composition was used as the evaluation for the feeling of use and the moisturizing effect. The sensory evaluation was performed for (1) osmotic sensation and (2) presence or absence of stickiness. The results of the combination are shown in Table 1 ~ Race: The composition of the vesicles shown in the beauty liquid 4 is observed under the observation of the Maltese 〇 beauty liquid, applied to the skin, specifically 'by professional investigators, and (3) moisturizing effect, ^ 4 is shown. -13- 200922631 [Table i]

No. 成分 本發明品 1 2 3 4 5 6 7 1 來自大豆的氫化溶血磷脂質 1 0.01 5 1 1 1 1 2 來自大豆的氫化磷脂質 _ _ _ _ 3 油醇 1 0.01 1 0.2 1 2 0.1 4 異硬脂酸 _ _ _ _ _ 5 硬脂醇 _ _ _ _ _ 6 膽固醇 1 0.01 1 1 0.25 2 0.1 7 植物甾醇 _ • _ «. • 8 1,3-丁二醇 10 10 10 10 10 10 10 9 甘油 10 10 10 10 10 10 10 10 精製水 剩餘量 剩餘量 剩餘量 剩餘量 剩餘量 剩餘量 剩餘量 11 三仙膠 0.2 0.2 0.2 0.2 0.2 0.2 0.2 12 乳酸鈉 _ — _ _ _ 13 香料 適量 適量 適量 適量 適量 適量 適量 成分(b)/成分(c) 1 1 1 0.2 4 1 1 成分(a)/[成分(b)+成分(c)] 0.5 0.5 2.5 0.83 0.8 0.25 5 評 估 項 巨 囊泡保存安定性 ◎ ◎ ◎ 〇 〇 〇 〇 滲透感 ◎ ◎ ◎ 〇 〇 ◎ ◎ 有無發黏 ◎ ◎ 〇 ◎ 〇 ◎ ◎ 保濕效果 ◎ 〇 ◎ 〇 〇 ◎ 〇 導電度(s/m) 0.03 0.03 0.03 0.03 0.03 0.03 0.03 注1 :溶血化率9 0 %、P C純度7 0 % 注2 : P C純度7 Ο % -14 - 200922631 [表2]No. Ingredients The present invention 1 2 3 4 5 6 7 1 Hydrogenated lysophospholipid from soybean 1 0.01 5 1 1 1 1 2 Hydrogenated phospholipid derived from soybean _ _ _ _ 3 Olefin 1 0.01 1 0.2 1 2 0.1 4 Isostearic acid _ _ _ _ _ 5 Stearyl alcohol _ _ _ _ _ 6 Cholesterol 1 0.01 1 1 0.25 2 0.1 7 Phytosterol _ • _ «. • 8 1,3-butanediol 10 10 10 10 10 10 10 9 Glycerin 10 10 10 10 10 10 10 10 Refining water Residual amount Residual amount Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount 11 Sanxianjiao 0.2 0.2 0.2 0.2 0.2 0.2 0.2 12 Sodium lactate _ — _ _ _ 13 Flavor amount Appropriate amount and appropriate amount of ingredients (b) / component (c) 1 1 1 0.2 4 1 1 Ingredient (a) / [ingredient (b) + component (c)] 0.5 0.5 2.5 0.83 0.8 0.25 5 Evaluation of macrovesicle preservation stability ◎ ◎ ◎ 〇〇〇〇 〇〇〇〇 ◎ ◎ ◎ ◎ 〇〇 ◎ ◎ With or without sticky ◎ ◎ 〇 ◎ 〇 ◎ ◎ Moisturizing effect ◎ 〇 ◎ 〇〇 ◎ 〇 conductivity (s / m) 0.03 0.03 0.03 0.03 0.03 0.03 0.03 Note 1: Hemolysis rate is 90%, PC purity is 70% Note 2: PC purity is 7 Ο % -14 - 200922631 [Table 2]

No. 成分 本發明品 8 9 10 11 12 1 來自大豆的氫化溶血磷脂質 1 1 0.01 0.01 0.01 2 來自大豆的氫化磷脂質 _ _ _ _ _ 3 油醇 _ 1 0.01 0.01 0.01 4 異硬脂酸 1 _ 师 - 5 硬脂醇 - _ - 6 膽固醇 1 _ 0.01 0.01 0.01 7 植物甾醇 1 一 _ 8 1,3-丁二醇 10 10 10 10 10 9 甘油 10 10 10 10 10 10 精製水 剩餘量 剩餘量 剩餘量 剩餘量 剩餘量 11 三仙膠 0.2 0.2 0.2 0.2 0.2 12 乳酸鈉 • _ 3 0.2 10 13 香料 適量 適量 適量 適量 適量 成分(b)/成分(c) 1 1 1 1 1 成分⑷/[成分(b)+成分(c)] 0.5 0.5 0.5 0.5 0.5 評 估 項 巨 囊泡保存安定性 ◎ ◎ ◎ ◎ 〇 滲透感 ◎ ◎ ◎ ◎ ◎ 有無發黏 ◎ 〇 〇 ◎ 〇 保濕效果 ◎ ◎ ◎ 〇 ◎ 導電度(s/m) 0.03 0.03 0.75 0.05 2.5 注1 : 溶血化率9 0 %、P C純度7 0 % 注2 : P C純度7 0 % -15- 200922631 [表3] No. 成分 本發明品 13 14 15 16 17 1 來自大豆的氫化溶血磷脂質 0.005 0.002 0.12 0.12 0.12 2 來自大豆的氫化磷脂質 0.005 0.008 _ _ _ 3 油醇 0.01 0.01 0.01 0.01 0.05 4 異硬脂酸 _ . 一 _ • 5 硬脂醇 _ _ 6 膽固醇 0.01 0.01 0.01 0.01 0.01 7 植物甾醇 _ _ - 8 1,3-丁二醇 10 10 10 10 10 9 甘油 10 10 10 10 10 10 精製水 剩餘量 剩餘量 剩餘量 剩餘量 剩餘量 11 三仙膠 0.2 0.2 0.2 0.2 0.2 12 乳酸鈉 3 3 3 3 3 13 香料 適量 適量 滴量 適量 適量 成分(b)/成分(c) 1 1 1 0.1 5 成分⑷/[成分(b)+成分(c)] 0.25 0.15 6 1.09 2 評 估 項 a 囊泡保存安定性 ◎ 〇 〇 〇 〇 滲透感 〇 〇 〇 〇 〇 有無發黏 〇 〇 〇 〇 〇 保濕效果 〇 〇 ◎ ◎ ◎ 導電度(s/m) 0.75 0.75 0.75 0.75 0.75 注1 : 溶血化率9 0 %、P C純度7 0 % 注2 : P C純度7 0 % -16- 200922631 [表4]No. Ingredients The present invention 8 9 10 11 12 1 Hydrogenated lysophospholipid from soybean 1 1 0.01 0.01 0.01 2 Hydrogenated phospholipid from soybean _ _ _ _ _ 3 Oleic alcohol _ 1 0.01 0.01 0.01 4 Isostearic acid 1 _ Division - 5 Stearyl alcohol - _ - 6 Cholesterol 1 _ 0.01 0.01 0.01 7 Phytosterol 1 - 8 1,3-butanediol 10 10 10 10 10 9 Glycerin 10 10 10 10 10 10 Remaining amount of refined water remaining Remaining amount Remaining amount 11 Sanxianjiao 0.2 0.2 0.2 0.2 0.2 12 Sodium lactate• _ 3 0.2 10 13 Proper amount of the right amount of the right amount (b) / component (c) 1 1 1 1 1 Ingredient (4) / [ingredient (b )+Component (c)] 0.5 0.5 0.5 0.5 0.5 Evaluation of macrocapsule storage stability ◎ ◎ ◎ ◎ 〇 〇 ◎ ◎ ◎ ◎ ◎ ◎ 有 发 发 〇 〇 〇 〇 moisturizing effect ◎ ◎ ◎ 〇 ◎ ◎ Conductivity ( s/m) 0.03 0.03 0.75 0.05 2.5 Note 1: Hemolysis rate 90%, PC purity 70% Note 2: PC purity 70% -15- 200922631 [Table 3] No. Ingredients The present invention 13 14 15 16 17 1 Hydrogenated lysophospholipid from soybean 0.005 0.002 0.12 0.12 0.12 2 from soybean Hydrogenated phospholipids 0.005 0.008 _ _ _ 3 oleyl alcohol 0.01 0.01 0.01 0.01 0.05 4 isostearic acid _ . a _ • 5 stearyl _ _ 6 cholesterol 0.01 0.01 0.01 0.01 0.01 7 plant sterol _ _ - 8 1,3 - Butanediol 10 10 10 10 10 9 Glycerin 10 10 10 10 10 10 Refining water Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount 11 Sanxianjiao 0.2 0.2 0.2 0.2 0.2 12 Sodium lactate 3 3 3 3 3 13 Flavor amount Amount of appropriate amount (b) / component (c) 1 1 1 0.1 5 Component (4) / [ingredient (b) + component (c)] 0.25 0.15 6 1.09 2 Evaluation item a vesicle preservation stability ◎ osmosis 〇〇〇〇〇 〇〇〇〇〇 发 发 〇〇〇〇〇 ◎ ◎ ◎ Conductivity (s / m) 0.75 0.75 0.75 0.75 0.75 Note 1: Hemolysis rate of 90%, PC purity 70% Note 2 : PC purity 70% -16- 200922631 [Table 4]

No. 成分 比較品 1 2 3 4 5 1 來自大豆的氫化溶血磷脂質 _ 1 1 1 _ 2 來自大豆的氫化磷脂質 - 1 3 油醇 1 _ 1 • 1 4 異硬脂酸 _ _ - _ 5 硬脂醇 _ 1 6 膽固醇 1 1 _ 1 1 7 植物甾醇 _ _ _ _ 8 1,3-丁二醇 10 10 10 10 10 9 甘油 10 10 10 10 10 10 精製水 剩餘量 剩餘量 剩餘量 剩餘量 剩餘量 11 三仙膠 0.2 0.2 0.2 0.2 0.2 12 乳酸鈉 _ _ _ _ 13 香料 適量 適量 適量 適量 適量 成分(b)/成分(c) 1 _ . 1 成分⑻/[成分(b)+成分(c)] - 1 1 1 _ 評 估 項 巨 囊泡保存安定性 X X Δ Δ X 滲透感 X Δ 〇 Δ 〇 有無發黏 X 〇 〇 〇 〇 保濕效果 X Δ X Δ 〇 導電度(s/m) 0.03 0.03 0.03 0.03 0.03 (製造方法) A:加熱成分(1)〜(9)成80°C。 B :以8 0 °C加熱溶解成分(1 0 )及(1 1 )。 C:添加A於B,以分散攪拌機(disper mixer)混合 攪拌,形成囊泡。 D :將C冷卻至室溫後,添加成分(12 )及(1 3 ), 得到囊泡組成物。 -17- 200922631 (評估方法:囊泡之保存安定性) 確認囊泡之安定性係於偏光顯微鏡下進行。以囊泡組 成物剛調製後之狀態爲基準,與40°C恆溫下經過2個月者 之狀態進行比較。關於經時觀察所確認之馬耳他十字像的 量係使用下述(i ) 4階段判定基準而判定。 (i ) 4階段判定基準 (判定):(評估) ◎:可確認80%以上之馬耳他十字像的量。 〇:可確認6 0 %以上,未滿8 0 %之馬耳他十字像的量 〇 △:可確認3 0 %以上,未滿6 0 %之馬耳他十字像的量 〇 X :可確認未滿30%之馬耳他十字像的量。 (評估方法:使用感及保濕效果) 使20位20〜40歲女性調查員使用調製之囊泡組成物 作爲美容液,關於作爲使用感之(1 )滲透感、(2 )有無 發黏、及(3 )保濕效果,依據以下(ii ) 5階段評估基準 ’進行官能評估,另外,依據(iii ) 4階段判定基準,判 定總調查員評分之平均値。 (ii ) 5階段評估基準 -18- 200922631 (評估) :(評分) 非常有感覺 ·· 5分 稍微感覺得到 :4分 普通 ·_ 3分 不太有感覺 :2分 無感覺 ·· 1分 (iii ) 4階段判定基準 (總調查員評分之平均値) :(判定) 平均分爲4,5以上 :◎ 平均分爲3.5以上,未滿4.5 :〇 平均分爲2 · 5以上,未滿3.5 : △No. Ingredient comparison product 1 2 3 4 5 1 Hydrogenated lysophospholipid from soybean _ 1 1 1 _ 2 Hydrogenated phospholipid derived from soybean - 1 3 oleyl alcohol 1 _ 1 • 1 4 isostearic acid _ _ - _ 5 Stearyl alcohol _ 1 6 Cholesterol 1 1 _ 1 1 7 Phytosterol _ _ _ _ 8 1,3-butanediol 10 10 10 10 10 9 Glycerin 10 10 10 10 10 10 Refining water remaining amount remaining amount remaining amount remaining Remaining amount 11 Sanxianjiao 0.2 0.2 0.2 0.2 0.2 12 Sodium lactate _ _ _ _ 13 Proper amount of the right amount of the right amount of ingredients (b) / component (c) 1 _ . 1 ingredient (8) / [component (b) + component (c) ] - 1 1 1 _ Evaluation item vesicle preservation stability XX Δ Δ X osmotic sensation X Δ 〇 Δ 〇 presence or absence of viscosity X 〇〇〇〇 moisturizing effect X Δ X Δ 〇 conductivity (s/m) 0.03 0.03 0.03 0.03 0.03 (Manufacturing method) A: The components (1) to (9) were heated to 80 °C. B: The components (10) and (1 1 ) were dissolved by heating at 80 °C. C: A was added to B, and the mixture was stirred and mixed with a disper mixer to form vesicles. D: After cooling C to room temperature, components (12) and (13) were added to obtain a vesicle composition. -17- 200922631 (Evaluation method: preservation stability of vesicles) It was confirmed that the stability of vesicles was carried out under a polarizing microscope. Based on the state immediately after the preparation of the vesicle composition, it was compared with the state of 2 months at a constant temperature of 40 °C. The amount of the Maltese cross image confirmed by the observation of time was determined using the following (i) 4-stage determination criteria. (i) 4-stage judgment standard (judgment): (evaluation) ◎: The amount of Maltese cross image of 80% or more can be confirmed. 〇: It can be confirmed that the amount of Maltese cross image is more than 60%, less than 80%. △: It can be confirmed that more than 30%, the amount of Maltese cross image less than 60% 〇X: Can confirm less than 30% The amount of the Maltese cross. (Evaluation method: sensation and moisturizing effect) 20 female 20- to 40-year-old female investigators used the prepared vesicle composition as a cosmetic liquid, and (1) osmotic feeling, (2) presence or absence of stickiness, and (3) The moisturizing effect is evaluated according to the following (ii) 5-stage evaluation criteria', and the average 値 of the total investigator's score is determined according to the (iii) 4-stage determination criteria. (ii) 5-stage evaluation benchmark -18- 200922631 (evaluation): (score) Very sensational·· 5 points slightly felt: 4 points normal _ 3 points not feeling: 2 points no feeling · 1 point ( Iii) 4-stage decision criteria (average 总 of the total investigator's score): (Judgement) The average score is 4, 5 or more: ◎ The average score is 3.5 or more, less than 4.5: The average score is 2 · 5 or more, less than 3.5 : △

平均分未滿2.5 : X (評估方法:導電度) 使用導電度計(東亞電波工業社製導電度計 CM _ 60G )測定各試料於25 °C時之導電度。 由表1〜表4之結果顯示,本發明品1〜1 7係於4 〇 °c 之恆溫下二個月之安定性優異。另外,作爲美容液塗佈於 皮膚時,爲滲透感優異、不發黏之使用感、保濕效果優異 者。 另一方面,不含有成分(a)之比較品1未成形囊泡 。另外,不含有成分(b)及成分(c)之比較品2及3、 或含有硬脂醇以取代成分(c )之比較品4、含有磷脂質以 -19 - 200922631 取代成分(a )之比較品5雖然形成囊泡,但任一種皆於 _時觀察時,觀察到膽固醇之結晶析出或沈澱等之保存安 定性上有問題。 [實施例2 :化粧水] (成分) (%) 1·來自蛋黃之氫化溶血磷脂質(注3) 3.0 2 ·荷荷芭醇 0.8 3 ·植物甾醇 0.6 4-羥基硬脂酸膽固醇 0.2 5. 二丙二醇 1〇.〇 6. 精製水 剩餘量 7 -左旋絲胺酸 2.0 8.茶胺酸 2.0 9_甘油 5.0 10. 乙醇 5.0 11. 防腐劑 適量 12. 香料 適量 (注3 )溶血化率爲6 8 % ’ P C純度爲3 0 %。 (製法) A :以8 0 °C加熱溶解成分(1 )〜(5 )。 B:加熱成分(6)成80°C ° C :添加A於B,於混合攪拌下’使形成囊泡,冷卻 -20- 200922631 至室溫。 D :添加成分(7 )〜(12 )於C,得到化粧水。 實施例2之化粧水係囊泡之保存安定性良好,滲透感 優異、不發黏、保濕效果優異之皮膚外用劑。另外,導電 度爲 0.05s/m。 [實施例3 :水中油型乳液] (成分) (%) 1. 三十六烯烷(Squalane) 5.0 2. 十甲基環五矽氧烷 5.0 3 .聚環氧乙烷(6 0 )硬化箆麻油 2.0 4.硬脂酸十六醇(Cetostearyl Alcohol) 0.5 6.1,3 -丁二醇 7.0 7. 甘油 5.0 8. 丙烯酸-甲基丙烯酸烷基酯共聚物(注4) 0.2 9. 防腐劑 適量 1 0 ·三乙醇胺 0.2 1 1 .乙二胺四乙酸二鈉 0.02 1 2 .精製水 剩餘量 1 3 .香料 適量 1 4.來自大豆之氫化溶血磷脂質(注5 ) 0.5 1 5 .氫化大豆磷脂質 0.1 1 6 .辛基十二烷醇 1.0 1 7.膽固醇 0.6 -21 - 200922631 1 8.二丙二醇 7.0 1 9.精製水 10.0 (注 4 ) Pemulen TR-2 ( NOVEON 社製) (注5 )溶血化率爲88%,PC純度爲80% (製造方法) A:加熱溶解成分(1)〜(7)成70°C。 B:加熱成分(8)〜(12)成70 °C後’添加於A,進 行乳化。 C :將B冷卻至室溫。 D :以8 0 °C加熱溶解成分(1 4 )〜(1 8 )。 E :加熱成分(19 )成8 0 °C ’添加D下’混合攪拌’ 形成囊泡。 F :冷卻E後,添加於C ’再添加成分(1 3 ) ’得到 水中油型乳液。 實施例3之水中油型乳液係囊泡之保存安定性良好’ 滲透感優異、不發黏、保濕效果優異之皮膚外用劑。另外 ’導電度爲〇 . 02s/m。 [實施例4 :水中油型乳霜] (成分) (%) 1. 氫化大豆磷脂質 2-〇 2. 三硬脂酸聚環氧乙烷(20)山梨糖醇酐 3_0 3. 硬脂醇 5·0 -22- 200922631 4. 流動鏈烷烴 10.0 5. 夏威夷火山豆油 5.0 6. 硬化油 3.0 7. 甘油 10.0 8. 精製水 剩餘量 9. 乙醇 5.0 1 〇.防腐劑 適量 1 1 .香料 適量 1 2 ·來自大豆之氫化溶血磷脂質(注1 ) 3.0 13.癸基四癸基醇 0.4 1 4 ·植物甾醇 1.0 1 5 .丙二醇 10.0 1 9.精製水 10.0 (製法) A :以7 (TC加熱溶解成分(1 )〜(6 )。The average score is less than 2.5 : X (Evaluation method: Conductivity) The conductivity of each sample at 25 ° C was measured using a conductivity meter (Conductivity meter CM _ 60G manufactured by Toa Denki Kogyo Co., Ltd.). From the results of Tables 1 to 4, it is shown that the products 1 to 17 of the present invention are excellent in stability at a constant temperature of 4 〇 °c for two months. In addition, when it is applied to the skin as a cosmetic liquid, it is excellent in a feeling of penetration, a feeling of not sticky, and an excellent moisturizing effect. On the other hand, the comparative product 1 which does not contain the component (a) has no formed vesicles. Further, the comparative products 2 and 3 which do not contain the component (b) and the component (c), or the comparative product 4 which contains stearyl alcohol in place of the component (c), and the phospholipid-containing compound -19 - 200922631 are substituted for the component (a) Although the comparative product 5 formed a vesicle, when it was observed at the time of _, it was observed that there was a problem in the preservation stability of crystal precipitation or precipitation of cholesterol. [Example 2: lotion] (ingredient) (%) 1. Hydrogenated lysophospholipid from egg yolk (Note 3) 3.0 2 · Jojobaol 0.8 3 · Phytosterol 0.6 4-hydroxystearic acid cholesterol 0.2 5. Dipropylene glycol 1〇.〇6. Remaining amount of refined water 7 - L-serine 2.0 8. Theanine 2.0 9_glycerol 5.0 10. Ethanol 5.0 11. Preservative amount 12. Spice amount (Note 3) Hemolysis rate 6 8 % 'PC purity is 30%. (Preparation method) A: The components (1) to (5) are dissolved by heating at 80 °C. B: Heating the component (6) to 80 ° C ° C: Add A to B, and mix under stirring to form a vesicle, and cool -20-200922631 to room temperature. D: Add the ingredients (7) to (12) to C to obtain a lotion. The lotion-based vesicles of Example 2 have excellent storage stability, excellent skin penetration, and are not sticky, and have a moisturizing effect. In addition, the conductivity was 0.05 s/m. [Example 3: Oil-in-water emulsion] (Component) (%) 1. Triacontane (Squalane) 5.0 2. Decamethylcyclopentaoxane 5.0 3. Polyethylene oxide (60) hardening Castor oil 2.0 4. Cetostearyl Alcohol 0.5 6.1, 3-butanediol 7.0 7. Glycerin 5.0 8. Acrylic acid-alkyl methacrylate copolymer (Note 4) 0.2 9. Preservatives 1 0 · Triethanolamine 0.2 1 1 . Ethylenediaminetetraacetic acid disodium 0.02 1 2 . Remaining water residual amount 1 3 . Flavor amount 1 4. Hydrogenated lysophospholipid from soybean (Note 5) 0.5 1 5 . Hydrogenated soybean phospholipid Quality 0.11 6. Octyldodecanol 1.0 1 7. Cholesterol 0.6 -21 - 200922631 1 8. Dipropylene glycol 7.0 1 9. Refined water 10.0 (Note 4) Pemulen TR-2 (manufactured by NOVEON Co., Ltd.) (Note 5) The hemolytic rate was 88%, and the PC purity was 80% (manufacturing method) A: The dissolved components (1) to (7) were heated to 70 °C. B: The components (8) to (12) were heated to 70 ° C and then added to A to be emulsified. C: Cool B to room temperature. D: The component (1 4 ) to (1 8 ) was dissolved by heating at 80 °C. E: The heating component (19) was formed into a vesicle at 80 ° C 'adding D 'mixing and stirring'. F: After cooling E, the component (1 3 ) was added to C ' to obtain an oily emulsion in water. The oil-in-water emulsion type vesicle of Example 3 has good preservation stability. The skin external preparation is excellent in osmotic feeling, and is not sticky and has a moisturizing effect. In addition, the conductivity is 〇. 02s/m. [Example 4: oil-type cream in water] (ingredient) (%) 1. Hydrogenated soybean phospholipid 2-〇2. Tristearic acid polyethylene oxide (20) sorbitan 3_0 3. Stearyl alcohol 5·0 -22- 200922631 4. Flowing paraffin 10.0 5. Hawaii volcanic soybean oil 5.0 6. Hardened oil 3.0 7. Glycerin 10.0 8. Remaining amount of refined water 9. Ethanol 5.0 1 〇. Preservative amount 1 1 . 2 · Hydrogenated lysophospholipid from soybean (Note 1) 3.0 13. Mercaptotetradecyl alcohol 0.4 1 4 · Phytosterol 1.0 1 5 . Propylene glycol 10.0 1 9. Refined water 10.0 (manufacturing method) A : 7 (TC heating) Dissolve the components (1) to (6).

B :以7 0 °C加熱溶解成分(7 ) 、( 8 )後,添加於A ,進行乳化。 C :將B冷卻至室溫後,添加成分(9 )〜(1 1 )。 D :以8 (TC加熱溶解成分(1 2 )〜(1 5 )。 E :加熱成分(1 6 )成8 0 °C,添加D下,混合攪拌, 形成囊泡。 F :冷卻E後,添加於C,得到乳霜。 實施例4之水中油型乳霜係囊泡之保存安定性良好, -23- 200922631 滲透感優異、不發黏、保濕效果優異之皮膚外用劑。另外 ,導電度爲〇.〇7s/m。 [實施例5 :薄片狀化粧料] (成分) (%) 1 ·來自蛋黃之氫化溶血磷脂質(注3 ) 2.0 2. 油醇 0.5 3. 膽固醇 0.5 4. 異硬脂酸 0.2 5. 香料 0.1 6. 二甘油 5.0 7. 二丙二醇 10.0 8. 精製水 剩餘量 9. 對羥基苯甲酸甲酯 0.1 1 0. 乙醇 5.0 1 1 .抗壞血酸葡糖苷 3.0 1 2 .吡咯烷酮羧酸鈉 2.0 13.透明質酸鈉 0.2 1 4 .氫氧化鈉 0.13 (製法) A :以8 0 °C加熱溶解成分(1 )〜(7 )。 B :加熱成分(8 )成8 (TC,添加A下,混合攪拌, 形成囊泡。 -24- 200922631 c :冷卻B後,添加成分(9 )〜(14 ),含浸此於不 織布。 D :將C密封塡充於鋁層合之袋狀容器,得到薄片狀 化粧料。 實施例5之薄片狀化粧料係囊泡之保存安定性良好, 滲透感優異、不發黏、保濕效果優異之皮膚外用劑。另外 ,導電度爲1 .1 8s/m。 [實施例6 :水中油型乳霜狀打底化粧料] (成分) (%) 1 .氧化鋅(粒徑爲2 00nm ) 2.0 2. 二甲基聚矽氧烷 30.〇 3. 聚環氧乙烷(30)膽固醇醚 1.0 4. 棕櫚酸辛酯 1.5 5. 丙烯基-聚矽氧烷系接枝共聚物混合物(注6) 2.0 6_精製水 剩餘量 7. 乙醇 5.0 8. 丙二醇 5.0 9. 二氧化矽粉末 2.0 1 0.防腐劑 適量 1 1 .香料 適量 12. 來自大豆之氫化溶血磷脂質(注5) 0.2 13. 油酸 0.05 1 4.膽固醇 0.1 -25- 200922631 15. 1,3-丁二醇 2〇 16. 精製水 5.0 (注6 ) KP-543 (丙烯基一聚矽氧烷系接枝共聚物 50% :醋酸丁酯50%之混合物,信越化學工業社製) (製造方法) A :以3輥混合機分散處理成分(1 )〜(5 )。 B:均勻混合成分(6)〜(11)。 C :添加於A於B,進行乳化。 D :以8(TC加熱溶解成分(12)〜(15)。 E :加熱成分(16 )成8 0 °C ’添加D下’混合攪拌’ 形成囊泡。 F :冷卻E後,添加於C ’得到水中油型乳霜狀打底 化粧料。 實施例6之水中油型乳霜狀打底化粧料液係囊泡之保 存安定性良好,滲透感優異、不發黏、保濕效果優異之皮 膚外用劑。另外,導電度爲0.13 s/m。 -26-B: The components (7) and (8) were dissolved by heating at 70 ° C, and then added to A to carry out emulsification. C: After cooling B to room temperature, components (9) to (1 1 ) were added. D: The component (1 2 ) to (1 5 ) was dissolved by heating at 8 (TC). E: The heating component (1 6 ) was added to 80 ° C, and D was added and stirred to form a vesicle. F: After cooling E, It is added to C to obtain a cream. The oil-based cream of Example 4 has good storage stability, -23- 200922631 Skin external preparation excellent in penetration, non-stickiness, and moisturizing effect. 〇.〇7s/m. [Example 5: Flaky cosmetic] (ingredient) (%) 1 · Hydrogenated lysophospholipid from egg yolk (Note 3) 2.0 2. Oleic alcohol 0.5 3. Cholesterol 0.5 4. Different Stearic acid 0.2 5. Perfume 0.1 6. Diglycerin 5.0 7. Dipropylene glycol 10.0 8. Remaining amount of purified water 9. Methylparaben 0.1 1 0. Ethanol 5.0 1 1 . Ascorbyl glucoside 3.0 1 2 Pyrrolidone carboxylate Sodium 2.0 12. Sodium hyaluronate 0.2 1 4 . Sodium hydroxide 0.13 (Preparation method) A: The components (1) to (7) are dissolved by heating at 80 ° C. B: The heating component (8 ) is 8 (TC, Adding A, mixing and stirring to form vesicles. -24- 200922631 c : After cooling B, add ingredients (9) to (14), impregnate the non-woven fabric. D: Fill the C seal The flaky cosmetic of Example 5 is a flaky cosmetic. The flaky cosmetic of Example 5 is a skin external preparation which is excellent in storage stability, excellent in osmotic feeling, and which is not sticky and has a moisturizing effect. The conductivity was 1.18 s/m. [Example 6: Oil-based cream-like primer in water] (ingredient) (%) 1. Zinc oxide (particle size: 200 nm) 2.0 2. Dimethyl polymerization矽 30 30. 〇 3. Polyethylene oxide (30) Cholesterol ether 1.0 4. Octyl palmitate 1.5 5. Propylene-polyoxyalkylene graft copolymer mixture (Note 6) 2.0 6_Refined water remaining Amount 7. Ethanol 5.0 8. Propylene glycol 5.0 9. Ceria powder 2.0 1 0. Preservative amount 1 1 Perfume amount 12. Hydrogenated lysophospholipid from soybean (Note 5) 0.2 13. Oleic acid 0.05 1 4. Cholesterol 0.1 -25- 200922631 15. 1,3-butanediol 2〇16. Refined water 5.0 (Note 6) KP-543 (propylene-based polyoxyalkylene graft copolymer 50%: butyl acetate 50% Mixture, manufactured by Shin-Etsu Chemical Co., Ltd.) (Manufacturing method) A: The components (1) to (5) are dispersed and processed in a 3-roll mixer. B: The components (6) to (11) are uniformly mixed. Applied to the A to B, emulsified. D: Dissolve the components (12) to (15) with 8 (TC). E: Heat the component (16) to 80 °C 'Add a mixture of 'mixing and stirring' to form vesicles. F: After cooling E, add to C 'Oilable oil-based cream-like primer for the water. The oil-based creamy base-based cosmetic liquid of Example 6 has good preservation stability, excellent penetration, no stickiness, and excellent moisturizing effect. External use agent. In addition, the conductivity is 0.13 s/m.

Claims (1)

200922631 十、申請專利範圍 1 · 一種囊泡組成物,其特徵爲含有下述成分(a )〜 (d); (a )溶血磷脂質 (b ) 1種或2種以上選自於2 5 °C爲液狀之高級醇或 液狀之高級脂肪酸 (c )膽固醇或植物甾醇 (d )精製水 2. 如申請專利範圍第1項之囊泡組成物,其中更含 有成分(e )電解質。 3. 如申請專利範圍第1項或第2項之囊泡組成物, 其中成分(b)及成分(c)之含有質量比(b) / (c)爲 0 2 〜4。 4. 如申請專利範圍第1項至第3項中任一項之囊泡 組成物’其中成分(a)、成分(b)及成分(c)之含有 質量比(a) /[(b) + (c)]爲 0.25〜5。 5 ·如申請專利範圍第1項至第4項中任一項之囊泡 組成物,其中成分(b )係1種或2種以上選自油醇、異 硬脂醇、油酸、及異硬脂酸。 6 ·如申請專利範圍第1項至第5項中任一項之囊泡 組成物,其於25 時之導電度爲0.02〜2.5 s/m。 7 · —種皮膚外用劑,其特徵係含有申請專利範圍第1 項至第6項中任一項之囊泡組成物。 -27- 200922631 七 明 說 單 簡 leu # 符 表 為代 圖件 表元 代之 定圖 指表 :案代 圖本本 表' ' 代} 3 定一二 指 /IX Γν 無 無 八、本案若有化學式時,請揭示最能顯示發明特徵的化學 式:無200922631 X. Patent Application No. 1 · A vesicle composition characterized by containing the following components (a) to (d); (a) lysophospholipid (b) 1 or more selected from 2 5 ° C is a liquid higher alcohol or liquid higher fatty acid (c) cholesterol or phytosterol (d) purified water 2. The vesicle composition of claim 1 which further contains the component (e) electrolyte. 3. For the vesicle composition of claim 1 or 2, the mass ratio (b) / (c) of the component (b) and the component (c) is 0 2 to 4. 4. The mass ratio of component (a), component (b) and component (c) of the vesicle composition of any one of claims 1 to 3 (a) / [(b) + (c)] is 0.25~5. The vesicle composition according to any one of the items 1 to 4, wherein the component (b) is one or more selected from the group consisting of oleyl alcohol, isostearyl alcohol, oleic acid, and Stearic acid. 6. The vesicle composition according to any one of claims 1 to 5, which has a conductivity of 0.02 to 2.5 s/m at 25 o'clock. A skin external preparation characterized by comprising the vesicle composition according to any one of claims 1 to 6. -27- 200922631 七明说单简 leu # 符表 is the generation of map elements on behalf of the map refers to the table: the case map this table ' ' generation} 3 fixed one or two fingers / IX Γ 无 no eight, the case if there is a chemical formula Please reveal the chemical formula that best shows the characteristics of the invention: none
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