JPH08133944A - Skin external agent for beautifully whitening - Google Patents

Skin external agent for beautifully whitening

Info

Publication number
JPH08133944A
JPH08133944A JP6293793A JP29379394A JPH08133944A JP H08133944 A JPH08133944 A JP H08133944A JP 6293793 A JP6293793 A JP 6293793A JP 29379394 A JP29379394 A JP 29379394A JP H08133944 A JPH08133944 A JP H08133944A
Authority
JP
Japan
Prior art keywords
acid
ester
phosphatidyl
skin
whitening
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP6293793A
Other languages
Japanese (ja)
Inventor
Megumi Yoshioka
恵 吉岡
Atsuhiro Iwamoto
敦弘 岩本
Akira Tsunoda
昭 角田
Sumitaka Kokusho
純孝 国生
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Meito Sangyo KK
Noevir Co Ltd
Original Assignee
Meito Sangyo KK
Noevir Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Meito Sangyo KK, Noevir Co Ltd filed Critical Meito Sangyo KK
Priority to JP6293793A priority Critical patent/JPH08133944A/en
Publication of JPH08133944A publication Critical patent/JPH08133944A/en
Pending legal-status Critical Current

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  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

PURPOSE: To obtain a safe and stable skin external agent for beautifully whitening the skin, inhibiting the tyrosinase biosynthesis of melanocyte to prevent the production of melanin, exhibiting an excellent beautifully whitening action and low in skin irritability by compounding an α-hydroxy acid compound. CONSTITUTION: This skin external agent for beautifully whitening the skin contains 0.001-10wt.% of one or more of the phosphatidyl ester and lysophosphatidyl ester of an α-hydroxy acid of formula I [A is group of formula II, etc.; B is group of formula III, etc.; (R1 , R2 are both fatty acid residues; R3 is H, an alkyl, etc.; X is an acyloxy, an amide); M is H, an alkali metal, etc.,] or its derivative. The conversion of the α-hydroxy acid, etc., into the phosphatidyl ester or lysophosphatidyl ester remarkably enhances the percutaneous permeability and cell membrane permeability of the acid, etc., and improves the tyrosinase biosynthesis-inhibiting action in the same compounding amount. The skin external agent exhibits an effective chromatodermatosis-improving effect in a small amount.

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【産業上の利用分野】本発明は、皮膚の色黒,シミ,ソ
バカス、或いは日焼けによる色素沈着を改善する美白用
皮膚外用剤に関する。さらに詳しくは、α-ヒドロキシ
酸又はその誘導体のホスファチジルエステル及びリゾホ
スファチジルエステルより選択した1種又は2種以上を
配合して、メラノサイトのチロシナーゼ生合成を阻害す
ることによりメラニン生成を抑制して、非常に有効な美
白作用を示し、且つ皮膚刺激性が低く、安全でさらに安
定である美白用皮膚外用剤に関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a whitening skin external preparation for improving pigmentation due to dark skin, dark spots, freckles, or sunburn. More specifically, by blending one or more selected from phosphatidyl ester and lysophosphatidyl ester of α-hydroxy acid or its derivative, and inhibiting melanin production by inhibiting tyrosinase biosynthesis of melanocytes, The present invention relates to a skin whitening external preparation that exhibits an effective whitening effect, is low in skin irritation, and is safe and stable.

【0002】[0002]

【従来の技術】従来より、皮膚の色黒,シミ,ソバカ
ス、或いは日焼けによる色素沈着等を改善する目的で、
美白用皮膚外用剤の開発が進められ、アスコルビン酸,
グルタチオン,コロイドイオウ等が有効成分として用い
られてきた。また、種々の薬用植物の抽出物や、植物由
来の没食子酸,ゲラニイン等を用いた例もある。最近で
は、コウジ酸やアルブチン等のハイドロキノンの配糖体
など、有効な美白成分が単離され、皮膚外用剤に配合さ
れている。
2. Description of the Related Art Conventionally, for the purpose of improving skin color darkness, stains, freckles, or pigmentation due to sunburn,
Development of a skin whitening external preparation was promoted, and ascorbic acid,
Glutathione, colloidal sulfur, etc. have been used as active ingredients. There are also examples in which extracts of various medicinal plants, plant-derived gallic acid, geraniin and the like are used. Recently, effective whitening ingredients such as hydroquinone glycosides such as kojic acid and arbutin have been isolated and incorporated into external skin preparations.

【0003】一方、グリコール酸,乳酸といったα-ヒ
ドロキシ酸が、メラノサイトのチロシナーゼ生合成を阻
害し、メラニン生成を抑制する作用を有することが古く
から報告されている。
On the other hand, it has long been reported that α-hydroxy acids such as glycolic acid and lactic acid have an action of inhibiting tyrosinase biosynthesis of melanocytes and suppressing melanin production.

【0004】しかしながら、アスコルビン酸は酸化され
やすく不安定であり、グルタチオンやコロイドイオウ
は、特有の異臭や沈澱を生じるという欠点を有する。ま
た、従来の薬用植物抽出物は、美白効果が不十分であっ
たり、品質が一定しないといった問題点を有していた。
さらに、コウジ酸等においても安定性上問題があり、他
の美白成分の中には連用により副作用の生じるものもあ
った。
[0004] However, ascorbic acid is easily oxidized and is unstable, and glutathione and colloidal sulfur have a disadvantage that they give off a peculiar offensive odor and precipitate. In addition, conventional medicinal plant extracts have problems that the whitening effect is insufficient and that the quality is not constant.
Further, kojic acid and the like also have a problem in stability, and some of the other whitening components cause side effects due to continuous use.

【0005】他方、α-ヒドロキシ酸のメラニン生成抑
制作用にはすばらしいものがあるが、これらは親油性が
低いため経皮透過性及び細胞膜透過性が低く、有効な美
白効果を発現させるためにはかなり高濃度を外用剤基剤
中に配合する必要があった。そのため、外用剤のpHが
低下して製剤の安定性に影響を及ぼしたり、皮膚に対す
る刺激性が生じたりして、好ましい美白用皮膚外用剤を
得ることは困難であった。
On the other hand, α-hydroxy acids have excellent melanin production-inhibiting action, but since they have low lipophilicity, they have low transdermal permeability and cell membrane permeability, and in order to exert an effective whitening effect. It was necessary to blend a fairly high concentration into the external preparation base. Therefore, the pH of the external preparation is lowered to affect the stability of the preparation, or the skin is irritated, so that it is difficult to obtain a preferable whitening skin external preparation.

【0006】[0006]

【発明が解決しようとする課題】本発明は上記の課題を
解決し、皮膚刺激性や副作用の問題がなく安全且つ安定
で、非常に優れた美白効果を発揮する美白用皮膚外用剤
を提供することを目的とする。すなわち、優れた美白効
果を有するα-ヒドロキシ酸又はその誘導体の経皮及び
細胞膜透過性を高めて、表皮基底層に存在するメラノサ
イトに有効濃度を到達させることを可能とするものであ
る。
DISCLOSURE OF THE INVENTION The present invention solves the above problems and provides a skin whitening external preparation which is safe and stable without causing skin irritation and side effects and exerts a very excellent whitening effect. The purpose is to That is, it is possible to increase the percutaneous and cell membrane permeability of α-hydroxy acid or its derivative having an excellent whitening effect, and to reach an effective concentration of melanocytes present in the basal layer of the epidermis.

【0007】[0007]

【課題を解決するための手段】本発明においては、α-
ヒドロキシ酸及びその誘導体の経皮及び細胞膜透過性を
高めるため、細胞膜構成成分であるホスファチジル基又
はリゾホスファチジル基をキャリヤーとして用いること
を試みた。その結果、α-ヒドロキシ酸等をホスファチ
ジルエステル又はリゾホスファチジルエステルとするこ
とにより、これらの経皮透過性は顕著に高まり、同一配
合量におけるチロシナーゼ生合成阻害作用が驚くほど向
上することを見い出した。従って、皮膚外用剤基剤に対
する前記α-ヒドロキシ酸等のホスファチジルエステル
及びリゾホスファチジルエステルの配合量は少量でよ
く、外用剤の製剤安定性に及ぼす影響も小さく、さらに
皮膚刺激の発生等安全性上の問題もない。
In the present invention, α-
In order to enhance the transdermal and cell membrane permeability of hydroxy acid and its derivatives, we tried to use phosphatidyl group or lysophosphatidyl group, which is a cell membrane constituent, as a carrier. As a result, it was found that by using α-hydroxy acid or the like as a phosphatidyl ester or a lysophosphatidyl ester, the transdermal permeability of these is significantly increased, and the tyrosinase biosynthesis inhibitory action at the same blending amount is surprisingly improved. Therefore, the compounding amount of the phosphatidyl ester such as α-hydroxy acid and lysophosphatidyl ester with respect to the skin external preparation base may be small, the influence on the formulation stability of the external preparation is small, and the safety such as the occurrence of skin irritation is improved. There is no problem.

【0008】α-ヒドロキシ酸又はその誘導体のホスフ
ァチジルエステルは、ホスファチジルコリン,大豆レシ
チン等を基質として、微生物由来のホスフォリパーゼD
によるホスファチジル基転移反応により効率良く得るこ
とができる。
The phosphatidyl ester of α-hydroxy acid or its derivative is a phospholipase D derived from a microorganism using phosphatidylcholine, soybean lecithin or the like as a substrate.
It can be efficiently obtained by the phosphatidyl group transfer reaction by.

【0009】たとえば、グリコール酸,グリセリン酸,
グルコン酸のホスファチジルエステルについては、特開
昭60−41494号公報記載の方法、乳酸のホスファ
チジルエステルについては特開昭59-187786号
公報記載の方法により製造することができる。すなわ
ち、ホスフォリパーゼDにより、リン脂質のホスファチ
ジン酸残基をα-ヒドロキシ酸又はその誘導体の水酸基
に転移させて製造することができる。
For example, glycolic acid, glyceric acid,
The phosphatidyl ester of gluconic acid can be produced by the method described in JP-A-60-41494, and the phosphatidyl ester of lactic acid can be produced by the method described in JP-A-59-187786. That is, it can be produced by transferring a phosphatidic acid residue of a phospholipid to a hydroxyl group of α-hydroxy acid or a derivative thereof with phospholipase D.

【0010】上記反応に用いるリン脂質としては、大
豆,卵黄レシチンのように植物又は動物由来のものや、
微生物由来のもの或いは合成リン脂質が使用でき、さら
に水素添加して硬化したリン脂質であってもよい。ま
た、ホスフォリパーゼDとしては、α-ヒドロキシ酸等
へホスファチジン酸残基を転移する能力のあるものであ
れば、どのような起源のものでもよい。
The phospholipids used in the above reaction include those derived from plants or animals such as soybean and egg yolk lecithin,
A phospholipid derived from a microorganism or a synthetic phospholipid can be used, and a phospholipid hardened by hydrogenation may be used. The phospholipase D may be of any origin as long as it has the ability to transfer a phosphatidic acid residue to α-hydroxy acid or the like.

【0011】具体的な転移反応は、リン脂質をエーテル
等の有機溶媒に溶かし、α-ヒドロキシ酸等の水溶液と
ホスフォリパーゼDを添加し、混合して行わせる。この
際、反応液にナトリウム塩,カリウム塩,カルシウム塩
或いはマグネシウム塩等の金属塩を加えることにより、
添加した金属塩に応じたホスファチジルエステルの塩が
得られる。反応後、溶液からホスファチジルエステルを
上記公報に記載された方法により回収し、必要に応じて
精製して、目的のα-ヒドロキシ酸等のホスファチジル
エステルを得る。
The specific transfer reaction is carried out by dissolving phospholipid in an organic solvent such as ether, adding an aqueous solution of α-hydroxy acid and phospholipase D, and mixing them. At this time, by adding a metal salt such as sodium salt, potassium salt, calcium salt or magnesium salt to the reaction solution,
A salt of the phosphatidyl ester is obtained depending on the metal salt added. After the reaction, the phosphatidyl ester is recovered from the solution by the method described in the above publication and, if necessary, purified to obtain the desired phosphatidyl ester such as α-hydroxy acid.

【0012】また、α-ヒドロキシ酸等のリゾホスファ
チジルエステルは、上記したα-ヒドロキシ酸等のホス
ファチジルエステルにホスフォリパーゼA1又はA2を作
用させ、ホスファチジル基のα位又はβ位の脂肪酸を加
水分解することにより調製できる。
Further, the lysophosphatidyl ester such as α-hydroxy acid is hydrolyzed to the above-mentioned phosphatidyl ester such as α-hydroxy acid with phospholipase A1 or A2 to hydrolyze the fatty acid at the α-position or β-position of the phosphatidyl group. It can be prepared by

【0013】本発明で用いるα-ヒドロキシ酸又はその
誘導体のホスファチジルエステル及びリゾホスファチジ
ルエステルの経皮透過性及びチロシナーゼ生合成阻害作
用について、α-ヒドロキシ酸として乳酸を用いた場合
の例を以下に示す。
Regarding the transdermal permeability and tyrosinase biosynthesis inhibitory action of phosphatidyl ester and lysophosphatidyl ester of α-hydroxy acid or its derivative used in the present invention, an example of using lactic acid as α-hydroxy acid is shown below. .

【0014】経皮透過性は、ホスファチジル乳酸,リゾ
ホスファチジル乳酸及び比較のため乳酸をそれぞれトリ
チウムでラベルし、経皮浸透セルに添加して、セルのモ
ルモット皮膚片を透過して皮膚片下の溶液中に溶出した
放射活性を、シンチレーションカウンターにて測定し、
皮膚片を透過して溶出した放射活性の割合を求めて評価
した。結果を図1に示す。
Percutaneous permeability is determined by labeling phosphatidyl lactic acid, lysophosphatidyl lactic acid, and lactic acid for comparison with tritium, and adding them to a percutaneous permeation cell, and permeating the guinea pig skin piece of the cell to obtain a solution under the skin piece. The radioactivity eluted in was measured with a scintillation counter,
The ratio of the radioactivity eluted through the skin pieces was calculated and evaluated. The results are shown in Fig. 1.

【0015】図1より、乳酸に比べてホスファチジル乳
酸及びリゾホスファチジル乳酸の経皮透過性が顕著に向
上していることが認められる。24時間後には、ホスフ
ァチジル乳酸については乳酸の4.2倍、リゾホスファ
チジル乳酸については乳酸の4.0倍の放射活性の溶出
が認められた。
From FIG. 1, it is recognized that the transdermal permeability of phosphatidyl lactic acid and lysophosphatidyl lactic acid is significantly improved as compared with lactic acid. After 24 hours, phosphatidyl lactic acid was observed to elute 4.2 times that of lactic acid, and lysophosphatidyl lactic acid was observed to elute 4.0 times that of lactic acid.

【0016】チロシナーゼ生合成阻害作用の評価は次の
ようにして行った。ホスファチジル乳酸とリゾホスファ
チジル乳酸のエタノール溶液及び乳酸水溶液を、マウス
B16メラノーマ細胞の懸濁液(細胞数50,000程
度)に添加し、3日間培養を行った後、以下の方法によ
り細胞中のチロシナーゼ活性を測定した。すなわち、1
/15Mリン酸緩衝液(pH6.8)2mlに1.0重
量%のドーパ水溶液0.5ml及び培養細胞液0.5m
lを混合し、37℃にて1時間インキュベートした後、
405nmにおける吸光度(As)を測定した。対照と
して、溶媒のエタノール又は精製水のみを同様に添加し
て培養し、同様に培養細胞液とドーパ水溶液とをインキ
ュベートして吸光度(Ab)を測定し、次式によりチロ
シナーゼ生合成阻害率を求めた。ホスファチジル乳酸,
リゾホスファチジル乳酸及び乳酸の添加量を終濃度にし
て1.0mM〜80mMの範囲で変化させ、ドーズリス
ポンスを求めて図2に示した。
The tyrosinase biosynthesis inhibitory effect was evaluated as follows. An ethanol solution of phosphatidyl lactic acid and lysophosphatidyl lactic acid and an aqueous lactic acid solution were added to a suspension of mouse B16 melanoma cells (the number of cells was about 50,000), and the cells were cultured for 3 days, and then tyrosinase in the cells was cultured by the following method. The activity was measured. That is, 1
0.5 ml of 1.0 wt% dopa aqueous solution and 0.5 m of cultured cell fluid in 2 ml of 15/15 M phosphate buffer (pH 6.8)
l were mixed and incubated at 37 ° C. for 1 hour,
Absorbance (As) at 405 nm was measured. As a control, only the solvent ethanol or purified water was added in the same manner and the cells were cultured. Similarly, the cultured cell solution and the dopa aqueous solution were incubated to measure the absorbance (Ab), and the tyrosinase biosynthesis inhibition rate was calculated by It was Phosphatidyl lactic acid,
The final doses of lysophosphatidyl lactic acid and lactic acid were varied within the range of 1.0 mM to 80 mM, and the dose response was determined and shown in FIG.

【数1】 [Equation 1]

【0017】図2において、ホスファチジル乳酸及びリ
ゾホスファチジル乳酸を添加した場合は、50%阻害濃
度(ID50)がそれぞれ5.4mM及び6.5mMであ
るのに対し、乳酸を添加した場合のID50は24.0m
Mであった。従って、同一濃度を添加した場合、ホスフ
ァチジルエステル又はリゾホスファチジルエステルとす
ることによりチロシナーゼ生合成阻害率は大幅に向上す
る。
In FIG. 2, when phosphatidyl lactic acid and lysophosphatidyl lactic acid were added, the 50% inhibitory concentrations (ID50) were 5.4 mM and 6.5 mM, respectively, whereas the ID50 when lactic acid was added was 24. 0.0 m
It was M. Therefore, when the same concentration is added, the inhibition rate of tyrosinase biosynthesis is significantly improved by using phosphatidyl ester or lysophosphatidyl ester.

【0018】本発明に係る美白用皮膚外用剤は、ローシ
ョン状,ゲル状,乳剤,軟膏等の剤形とすることができ
る。また、柔軟性化粧水,収斂性化粧水,洗浄用化粧水
等の化粧水類、エモリエントクリーム,モイスチュアク
リーム,マッサージクリーム,クレンジングクリーム,
メイクアップクリーム等のクリーム類、エモリエント乳
液,モイスチュア乳液,ナリシング乳液,クレンジング
乳液等の乳液類、ゼリー状パック,ピールオフパック,
粉末状パック等のパック類、及び洗顔料類といった種々
の製剤形態の美白化粧料としても提供することができ
る。α-ヒドロキシ酸又はその誘導体のホスファチジル
エステルの配合量は0.001〜10重量%が適当であ
る。
The external whitening agent for whitening according to the present invention can be in the form of lotion, gel, emulsion, ointment and the like. In addition, softening lotion, astringent lotion, lotion such as wash lotion, emollient cream, moisture cream, massage cream, cleansing cream,
Creams such as make-up cream, emollient emulsions, moisturizing emulsions, nourishing emulsions, emulsions such as cleansing emulsions, jelly packs, peel-off packs,
It can also be provided as a whitening cosmetic in various formulations such as packs such as powder packs and face wash. The amount of the phosphatidyl ester of α-hydroxy acid or its derivative to be blended is preferably 0.001 to 10% by weight.

【0019】[0019]

【作用】本発明に係る美白用皮膚外用剤を連続して皮膚
に塗布すると、有効成分であるα-ヒドロキシ酸又はそ
の誘導体のホスファチジルエステル或いはリゾホスファ
チジルエステルは速やかに経皮吸収され、メラニン生合
成の行われるメラノサイトの分布する表皮基底層に到達
し、チロシナーゼの生合成を有効に阻害し、結果的に有
効なメラニン生成抑制作用を発揮する。従って、シミや
ソバカス或いは日焼けによる色素の沈着を改善し、さら
に日光紫外線等による色素の沈着を防止することができ
る。また、α-ヒドロキシ酸又はその誘導体のホスファ
チジルエステル或いはリゾホスファチジルエステルは少
量の配合で有効な作用を示すため、少量を配合するのみ
で所望の上記効果を発揮し、製剤の安定性に及ぼす影響
も少なく、皮膚刺激等安全性上の問題もない。
When the external preparation for whitening skin according to the present invention is continuously applied to the skin, the active ingredient, phosphatidyl ester or lysophosphatidyl ester of α-hydroxy acid or its derivative, is rapidly percutaneously absorbed and melanin biosynthesis occurs. It reaches the basal layer of the epidermis where melanocytes are distributed, effectively inhibits tyrosinase biosynthesis, and consequently exerts an effective melanin production suppressing action. Therefore, it is possible to improve the pigment deposition due to spots, freckles, or sunburn, and to prevent the pigment deposition due to sunlight and ultraviolet rays. In addition, since the phosphatidyl ester or lysophosphatidyl ester of α-hydroxy acid or a derivative thereof exhibits an effective action with a small amount of compounding, the desired above-mentioned effects can be exhibited even if only a small amount is compounded, and the influence on the stability of the preparation is also exerted. There are few safety problems such as skin irritation.

【0020】[0020]

【実施例】さらに本発明について、実施例により詳細に
説明する。まず、本発明で使用するα-ヒドロキシ酸の
ホスファチジルエステル及びリゾホスファチジルエステ
ルの製造例を示す。なお、他のα-ヒドロキシ酸のホス
ファチジル又はリゾホスファチジル誘導体についても、
下記の製造例と同様にして調製することができる。
EXAMPLES The present invention will be described in more detail with reference to Examples. First, production examples of phosphatidyl ester and lysophosphatidyl ester of α-hydroxy acid used in the present invention are shown. Regarding other phosphatidyl or lysophosphatidyl derivatives of α-hydroxy acid,
It can be prepared in the same manner as in the following production example.

【0021】[製造例1]卵黄レシチン(キューピー株
式会社製)20gをジエチルエーテル100mlに溶か
し、これに塩化ナトリウム4.0g,α-ヒドロキシ酸
20g,アクチノマデューラ(Actinomadura)属由来の
ホスフォリパーゼD(名糖産業株式会社製)1,000
単位を精製水100mlに溶解して加え、30℃で24
時間酵素反応を行わせた。反応終了後エーテル層を回収
し、エーテルを除去して転移反応後の総リン脂質20g
を回収した。このリン脂質を基準油脂分析試験法(日本
油化学協会編)のリン脂質組成分析法5.3.3.1-86により
分析した結果、転移反応により新たに生成したホスファ
チジルグリコール酸が80重量%、ホスファチジルグリ
セリン酸が50重量%、ホスファチジルグルコン酸が5
0重量%、ホスファチジル乳酸が40重量%含まれてい
た。
[Production Example 1] 20 g of egg yolk lecithin (Kewpie Co., Ltd.) was dissolved in 100 ml of diethyl ether, and 4.0 g of sodium chloride, 20 g of α-hydroxy acid, and phospholipase derived from the genus Actinomadura. D (Meito Sangyo Co., Ltd.) 1,000
Dissolve the unit in 100 ml of purified water and add it at 30 ° C for 24 hours.
The enzyme reaction was carried out for a time. After the reaction was completed, the ether layer was recovered, ether was removed, and 20 g of total phospholipid after the transfer reaction
Was recovered. This phospholipid was analyzed by the phospholipid composition analysis method 5.3.3.1-86 of the standard oil and fat analysis test method (edited by Japan Oil Chemistry Association). As a result, 80% by weight of phosphatidylglycolic acid newly generated by the transfer reaction and phosphatidylglyceric acid were generated. Is 50 wt% and phosphatidyl gluconic acid is 5
0% by weight and 40% by weight of phosphatidyl lactic acid were contained.

【0022】[製造例2]上記製造例1において得たホ
スファチジルグリコール酸10gをエーテル50mlに
再度溶解し、ホスフォリパーゼA2(ノボ・ノルディス
クバイオインダストリー株式会社製)水溶液10mlを
添加し、30℃,24時間反応させ、リン脂質のβ位脂
肪酸を加水分解した。反応終了後エーテル層を回収し、
エーテルを除去して総リン脂質8.2gを回収した。こ
のリン脂質を基準油脂分析試験法(日本油化学協会編)
のリン脂質組成分析法5.3.3.1-86により分析した結果、
加水分解反応により新たに生成したリゾホスファチジル
グリコール酸70重量%が含まれていた。
[Production Example 2] 10 g of the phosphatidyl glycolic acid obtained in Production Example 1 above was redissolved in 50 ml of ether, and 10 ml of an aqueous solution of phospholipase A2 (manufactured by Novo Nordisk Bioindustry Co., Ltd.) was added, and the mixture was heated to 30 ° C. For 24 hours to hydrolyze the β-position fatty acid of phospholipid. After the reaction is completed, the ether layer is collected,
The ether was removed to recover 8.2 g of total phospholipid. This phospholipid is used as a standard oil and fat analysis test method (edited by Japan Oil Chemistry Association)
As a result of analysis by the phospholipid composition analysis method 5.3.3.1-86 of
It contained 70% by weight of lysophosphatidyl glycolic acid newly formed by the hydrolysis reaction.

【0023】次いで、本発明に係る美白用クリームとし
て、実施例1〜5の処方を表1に示す。これらは、表1
中(1)〜(8)を75℃に加熱溶解し、これに75℃に加熱
溶解した(9)〜(11)及び(13)を加えて乳化し、冷却して
50℃にて(12)を添加し、さらに室温まで冷却して調製
する。
Next, Table 1 shows the formulations of Examples 1 to 5 as the whitening cream according to the present invention. These are shown in Table 1.
Medium (1) to (8) were dissolved by heating at 75 ° C, and (9) to (11) and (13) heated and dissolved at 75 ° C were added to this to emulsify, and the mixture was cooled at 50 ° C at (12). ) Is added, and it cools to room temperature, and it prepares.

【表1】 [Table 1]

【0024】実施例6〜10は美白用軟膏である。処方
を表2に示す。これらは、表2中(1)〜(5)の油相成分を
混合,溶解して均一とし、75℃に加熱したものを、
(6)を(7)に溶解して75℃に加熱したところに加えて乳
化し、冷却して調製する。
Examples 6 to 10 are whitening ointments. The prescription is shown in Table 2. These are obtained by mixing and dissolving the oil phase components (1) to (5) in Table 2 to make them uniform and heating to 75 ° C.
(6) is dissolved in (7), heated to 75 ° C., added to the mixture, emulsified, and cooled to prepare.

【表2】 [Table 2]

【0025】実施例11〜15は美白用乳液である。処
方を表3に示す。これらは、表3中(1)〜(7)を75℃に
加熱溶解し、これに75℃に加熱溶解した(8)〜(11)及
び(13)を添加して乳化し、冷却して50℃にて(12)を添
加し、さらに室温まで冷却して調製する。
Examples 11 to 15 are whitening emulsions. The prescription is shown in Table 3. In Table 3, (1) to (7) in Table 3 were heated and melted at 75 ° C, and (8) to (11) and (13) heated and melted at 75 ° C were added to emulsify and cool. It is prepared by adding (12) at 50 ° C. and further cooling to room temperature.

【表3】 [Table 3]

【0026】実施例16〜20は美白用化粧水である。
処方を表4に示す。これらは、表4中(1)〜(10)の各成
分を混合,溶解し、均一化して調製する。
Examples 16 to 20 are whitening lotions.
The prescription is shown in Table 4. These are prepared by mixing, dissolving and homogenizing the components (1) to (10) in Table 4.

【表4】 [Table 4]

【0027】上記の実施例について、使用試験により美
白効果を評価した。その際、各実施例で配合しているα
-ヒドロキシ酸等のホスファチジルエステル又はリゾホ
スファチジルエステルを、それぞれα-ヒドロキシ酸,
α-ヒドロキシ酸エステル或いはα-ヒドロキシ酸アミド
に代替したものを比較例とした。使用試験は、シミ,ソ
バカス,日焼け等の色素沈着が顕著に認められる30〜
50才代の女性パネラー20名ずつを1群とし、各群に
ついて実施例及び比較例の各試料をブラインドにて使用
させて行った。試料の使用は、毎日朝と夜の2回洗顔後
に適量を顔面に塗布させ、2カ月間継続させた。美白効
果は、使用試験終了後の顔面の色素沈着症状の程度を観
察して評価した。結果は表5〜8に示した。
The whitening effect of the above examples was evaluated by a usage test. At that time, α blended in each Example
-Phosphatidyl ester such as hydroxy acid or lysophosphatidyl ester is converted into α-hydroxy acid,
A substitute for α-hydroxy acid ester or α-hydroxy acid amide was used as a comparative example. In the use test, pigmentation such as spots, freckles, and sunburn was clearly observed.
20 female panelists in their 50s were set as one group, and each sample of Examples and Comparative Examples was blindly used for each group. The use of the sample was continued for 2 months by applying an appropriate amount to the face after washing twice each day in the morning and at night. The whitening effect was evaluated by observing the degree of facial pigmentation after the use test. The results are shown in Tables 5-8.

【0028】表5において、ホスファチジルグリコール
酸1.00重量%を配合した実施例1使用群では、全パ
ネラーにおいて色素沈着症状の改善が認められた。グリ
コール酸を配合した比較例1では、明確な改善の認めら
れたパネラーは半数にとどまっていた。グリセリン酸,
クエン酸,リンゴ酸ジエチルエステル及びクエン酸モノ
アミドを配合した比較例2〜5使用群では、これらα-
ヒドロキシ酸類の美白効果はかなり劣っているが、ホス
ファチジルエステルとして配合した実施例2〜5使用群
では、明らかに色素沈着症状の改善効果の向上が認めら
れた。
In Table 5, in the group used in Example 1 containing 1.00% by weight of phosphatidylglycolic acid, improvement in pigmentation symptoms was observed in all panelists. In Comparative Example 1 containing glycolic acid, the number of panelists in which a clear improvement was recognized was only half. Glyceric acid,
In the use groups of Comparative Examples 2 to 5 containing citric acid, malic acid diethyl ester and citric acid monoamide, these α-
Although the whitening effect of hydroxy acids is considerably inferior, the improvement effect of the pigmentation symptom was clearly recognized to be improved in the groups using Examples 2 to 5 in which the hydroxy acids were blended as the phosphatidyl ester.

【表5】 [Table 5]

【0029】表6においても同様の傾向が認められ、乳
酸,グリコール酸エチル,及びグリコール酸コレステリ
ルのホスファチジルエステルを配合した実施例6,7及
び10使用群では、全パネラーにおいて改善が認められ
た。グリコール酸コレステリルを配合した比較例10で
は、これがかなり良好な経皮透過性を有することから良
好な改善が認められるが、ホスファチジルエステルとす
ることにより、美白効果はさらに増強されていた。ホス
ファチジル乳酸,ホスファチジルクエン酸アミド及びホ
スファチジル乳酸プロピルエステルを配合した実施例9
使用群では、85%のパネラーにおいて明確な改善を示
した。また、ホスファチジルグルコン酸を配合した実施
例8使用群においても、グルコン酸を配合した比較例8
使用群に比べて、顕著な色素沈着症の改善が認められ
た。
The same tendency was observed in Table 6, and in the groups using Examples 6, 7 and 10 in which the phosphatidyl ester of lactic acid, ethyl glycolate and cholesteryl glycolate was added, improvement was observed in all panelists. In Comparative Example 10 in which cholesteryl glycolate was blended, a good improvement was observed because it had considerably good transdermal permeability, but the whitening effect was further enhanced by using the phosphatidyl ester. Example 9 containing phosphatidyl lactic acid, phosphatidyl citrate amide and phosphatidyl lactic acid propyl ester
The use group showed a clear improvement at 85% of panelists. Further, also in the use group of Example 8 containing phosphatidyl gluconic acid, Comparative Example 8 containing gluconic acid
A marked improvement in pigmentation was observed as compared with the use group.

【表6】 [Table 6]

【0030】表7においても、ホスファチジルエステル
とすることにより、各α-ヒドロキシ酸類の美白効果が
向上することが認められる。実施例使用群ではいずれも
全パネラーにおいて症状の改善が認められ、症状の変化
の認められないパネラーはいなかった。特に、ホスファ
チジルグリコール酸0.50重量%とホスファチジル乳
酸メチルエステル0.30重量%を配合した実施例11
と、1-アシルリゾホスファチジル乳酸0.80重量%を
配合した実施例12使用群では、ほぼ全員のパネラーに
おいて改善を認めていた。
Also in Table 7, it is recognized that the whitening effect of each α-hydroxy acid is improved by using the phosphatidyl ester. In all of the groups used in the examples, the symptoms were improved in all the panelists, and no panelists did not find any change in the symptoms. In particular, Example 11 in which 0.50% by weight of phosphatidylglycolic acid and 0.30% by weight of phosphatidyl lactic acid methyl ester were mixed.
In the group using Example 12 in which 0.80% by weight of 1-acyl lysophosphatidyl lactic acid was blended, almost all panelists recognized improvement.

【表7】 [Table 7]

【0031】表8においても、各実施例使用群では65
%以上のパネラーにおいて明確な改善が認められ、症状
の緩和されなかったパネラーは認められない。これに対
し、α-ヒドロキシ酸類をホスファチジルエステル又は
リゾホスファチジルエステルとしないで配合した比較例
使用群では、明確な改善の認められたパネラーは35%
以下にとどまり、症状の改善傾向の認められないパネラ
ーも存在していた。
In Table 8 as well, it is 65 in the use group of each example.
% Or more of the panelists had a clear improvement, and no panelists whose symptoms were not alleviated. On the other hand, in the group using the comparative examples in which α-hydroxy acids were not used as the phosphatidyl ester or the lysophosphatidyl ester, the panelists in which the clear improvement was observed were 35%.
There were some panelists who did not show any improvement in symptoms, as shown below.

【表8】 [Table 8]

【0032】なお、上記の使用期間において、いずれの
実施例を使用した群においても、痛み,かゆみ等の皮膚
刺激やアレルギー反応等の皮膚障害を訴えたパネラーは
いなかった。また、乳化状態の悪化や配合成分の沈降,
変質等も認められなかった。
No panelists complained of skin irritation such as pain and itch or skin disorder such as allergic reaction in any of the groups used in the above-mentioned use period. In addition, deterioration of the emulsified state and sedimentation of the blended components,
No alteration was observed.

【0033】[0033]

【発明の効果】以上詳述したように、本発明により、少
量の美白成分の配合で非常に優れた色素沈着症状を改善
し得る美白用皮膚外用剤を提供することができる。本発
明に係る美白用皮膚外用剤においては、有効成分である
α-ヒドロキシ酸類が良好に標的細胞である表皮基底層
のメラノサイトに到達でき、低濃度の配合で優れたメラ
ニン生成抑制作用を示す。従って、皮膚刺激性や感作性
の発現するおそれもなく、製剤の安定性に悪影響を及ぼ
すこともない。
INDUSTRIAL APPLICABILITY As described above in detail, according to the present invention, it is possible to provide a whitening skin external preparation capable of improving a very excellent pigmentation symptom by blending a small amount of a whitening component. In the external preparation for whitening skin according to the present invention, the active ingredient α-hydroxy acids can reach the melanocytes of the basal layer of the epidermis, which are the target cells, satisfactorily, and exhibit excellent melanin production-inhibiting action at a low concentration. Therefore, there is no risk of skin irritation or sensitization, and the stability of the preparation is not adversely affected.

【図面の簡単な説明】[Brief description of drawings]

【図1】ホスファチジル乳酸,1-アシルリゾホスファチ
ジル乳酸及び乳酸の経皮透過性を比較して示す図であ
る。
FIG. 1 is a diagram showing a comparison of transdermal permeability of phosphatidyl lactic acid, 1-acyl lysophosphatidyl lactic acid and lactic acid.

【図2】ホスファチジル乳酸,1-アシルリゾホスファチ
ジル乳酸及び乳酸のチロシナーゼ生合成阻害作用を比較
して示す図である。
FIG. 2 is a diagram showing a comparison of tyrosinase biosynthesis inhibitory effects of phosphatidyl lactic acid, 1-acyl lysophosphatidyl lactic acid and lactic acid.

【符号の説明】[Explanation of symbols]

1 ホスファチジル乳酸 2 1-アシルリゾホスファチジル乳酸 3 乳酸 1 Phosphatidyl lactic acid 21-Acyl lysophosphatidyl lactic acid 3 Lactic acid

───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 FI 技術表示箇所 A61K 38/00 ADA (72)発明者 角田 昭 東京都福生市武蔵台1−27−5 (72)発明者 国生 純孝 東京都国立市谷保7026−3─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification number Internal reference number FI Technical indication location A61K 38/00 ADA (72) Inventor Akira Tsunoda 1-27-5 (72) Musashidai, Fussa-shi, Tokyo ) Inventor Sumitaka Kokusei 7026-3 Taniho, National City of Tokyo

Claims (3)

【特許請求の範囲】[Claims] 【請求項1】 一般式(1)で示されるα-ヒドロキシ
酸又はその誘導体のホスファチジルエステル及びリゾホ
スファチジルエステルより選択した1種又は2種以上を
配合することを特徴とする、美白用皮膚外用剤。 【化1】
1. An external preparation for whitening skin, comprising one or more selected from a phosphatidyl ester and a lysophosphatidyl ester of an α-hydroxy acid represented by the general formula (1) or a derivative thereof. . Embedded image
【請求項2】 α-ヒドロキシ酸が、一般式(1)にお
いてBが式(2)の化合物であるグリコール酸、一般式
(1)においてBが式(3)の化合物である乳酸、一般
式(1)においてBが式(4)の化合物であるグリセリ
ン酸、及び一般式(1)においてBが式(5)の化合物
であるグルコン酸より選択されることを特徴とする、請
求項1に記載の美白用皮膚外用剤。 【化2】 【化3】 【化4】 【化5】
2. An α-hydroxy acid is glycolic acid in which B is a compound of formula (2) in general formula (1), lactic acid in which B is a compound of formula (3) in general formula (1), and In (1), B is selected from glyceric acid, which is a compound of formula (4), and in general formula (1), B is selected from gluconic acid, which is a compound of formula (5). A skin external preparation for whitening as described. Embedded image Embedded image [Chemical 4] Embedded image
【請求項3】 美白用皮膚外用剤が美白化粧料であるこ
とを特徴とする、請求項1又は請求項2に記載の美白用
皮膚外用剤。
3. The whitening skin external preparation according to claim 1 or 2, wherein the whitening skin external preparation is a whitening cosmetic composition.
JP6293793A 1994-11-02 1994-11-02 Skin external agent for beautifully whitening Pending JPH08133944A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP6293793A JPH08133944A (en) 1994-11-02 1994-11-02 Skin external agent for beautifully whitening

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP6293793A JPH08133944A (en) 1994-11-02 1994-11-02 Skin external agent for beautifully whitening

Publications (1)

Publication Number Publication Date
JPH08133944A true JPH08133944A (en) 1996-05-28

Family

ID=17799239

Family Applications (1)

Application Number Title Priority Date Filing Date
JP6293793A Pending JPH08133944A (en) 1994-11-02 1994-11-02 Skin external agent for beautifully whitening

Country Status (1)

Country Link
JP (1) JPH08133944A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004217584A (en) * 2003-01-16 2004-08-05 Naris Cosmetics Co Ltd Skin care preparation for external use
EP1383493A4 (en) * 2001-05-02 2005-09-21 Univ New York Inhibition of pigmentation by inhibition of fatty acid synthase

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1383493A4 (en) * 2001-05-02 2005-09-21 Univ New York Inhibition of pigmentation by inhibition of fatty acid synthase
JP2004217584A (en) * 2003-01-16 2004-08-05 Naris Cosmetics Co Ltd Skin care preparation for external use

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