JPH05201846A - External agent for skin - Google Patents
External agent for skinInfo
- Publication number
- JPH05201846A JPH05201846A JP1555392A JP1555392A JPH05201846A JP H05201846 A JPH05201846 A JP H05201846A JP 1555392 A JP1555392 A JP 1555392A JP 1555392 A JP1555392 A JP 1555392A JP H05201846 A JPH05201846 A JP H05201846A
- Authority
- JP
- Japan
- Prior art keywords
- skin
- agent
- caffeic acid
- external preparation
- glucoside
- 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.)
- Granted
Links
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は皮膚外用剤に関し、詳し
くは生きた細胞（メラノサイト）のメラニン形成系に直
接作用してメラニン生成を抑制するとともに、保存時あ
るいは使用時の安定性が良好で皮膚色素沈着症の予防お
よび改善に優れた皮膚外用剤を提供せんとするものであ
る。FIELD OF THE INVENTION The present invention relates to an external preparation for skin, more specifically, it directly acts on the melanogenic system of living cells (melanocytes) to suppress melanin production and has good stability during storage or use. It is intended to provide an external preparation for skin which is excellent in the prevention and amelioration of skin pigmentation.
【０００２】[0002]
【従来の技術】シミ・ソバカスや日焼け後の色素沈着
は、皮膚内に存在する色素細胞の活性化によりメラニン
生成が著しく亢進したものであり、中高年齢層の肌の悩
みの一つになっている。2. Description of the Related Art Pigmentation after freckles and sunburn is a marked increase in melanin production due to the activation of pigment cells in the skin, which is one of the troubles of the skin in middle-aged people. There is.
【０００３】一般に、メラニンは色素細胞の中で生合成
された酵素チロシナーゼの働きによってチロシンからド
ーパ、ドーパからドーパキノンに変化し、次いで５，６
−ジヒドロキシインドール等の中間体を経て形成される
ものとされている。[0003] In general, melanin is changed from tyrosine to dopa and from dopa to dopaquinone by the action of the enzyme tyrosinase biosynthesized in pigment cells, and then 5, 6
-It is supposed to be formed via an intermediate such as dihydroxyindole.
【０００４】従って、色黒の防止、改善にはメラニン生
成過程での活性阻害や既成メラニンの淡色漂白が必要で
あり、これに基づき従来から種々の美白成分が提案され
てきた。例えば、チロシナーゼ活性阻害に対してはグル
タチオンに代表される硫黄化合物が挙げられ、また淡色
漂白化に対しては、過酸化水素水、ヒドロキノンやビタ
ミンＣ等が用いられてきた。Therefore, in order to prevent or improve color black, it is necessary to inhibit the activity in the process of melanin production and to bleach existing melanin in a light color, and various whitening components have been proposed based on this. For example, sulfur compounds typified by glutathione have been used to inhibit tyrosinase activity, and hydrogen peroxide solution, hydroquinone, vitamin C and the like have been used for light color bleaching.
【０００５】[0005]
【発明の解決しようとする課題】ところが、これら従来
の成分は処方系中での安定性が極めて悪く、分解による
着色、異臭を生じたり、細胞あるいは生体レベルにおけ
る効果・効能は未だ不充分であった。また、ヒドロキノ
ンについては強い色白作用を有するものの非可逆的白
斑、かぶれを引き起こす等安全性面で問題がある。However, these conventional ingredients have extremely poor stability in a formulation system, cause discoloration due to decomposition, give off an offensive odor, and have insufficient effects at the cell or biological level. It was Further, although hydroquinone has a strong whitening effect, it has a safety problem such as causing irreversible white spots and rashes.
【０００６】このように、従来から用いられている成分
は効果・効能、安定性、安全性の点において不充分であ
り、真に実用的に満足できるものは得られていない。一
方、このような観点から、従来用いられている成分に代
わるものとしてカフェイン酸が開示されている（国際公
開ＷＯ ９１／０５５４３）が、前記問題を克服できる
ものではない。As described above, the conventionally used components are insufficient in effect / efficacy, stability, and safety, and no one that is truly practically satisfactory has been obtained. On the other hand, from this point of view, caffeic acid has been disclosed as an alternative to the conventionally used component (International Publication WO 91/05543), but it cannot overcome the above problems.
【０００７】本発明はかかる実状に鑑みてなされたもの
であって、メラニン生成を抑制し、充分な皮膚色素沈着
症の改善・治療等の薬理効果を有し、かつ安全に使用で
きる皮膚外用剤を提供することを課題とする。The present invention has been made in view of the above circumstances, and has an external preparation for skin that suppresses melanin production, has sufficient pharmacological effects such as improvement and treatment of skin pigmentation disease, and can be used safely. The challenge is to provide.
【０００８】[0008]
【課題を解決するための手段】本発明者らは、上記課題
を解決するため鋭意研究を重ねた結果、カフェイン酸配
糖体が、生きた色素細胞のメラニン生成に対し強力な抑
制効果を有することを突き止め、更に、これを外用剤基
剤中に一定濃度以上で配合せしめた時に、皮膚に対する
優れた色白効果を発現することを見いだし、これに基づ
き本発明を完成した。As a result of intensive studies to solve the above problems, the present inventors have found that caffeic acid glycoside has a strong inhibitory effect on melanin production in living pigment cells. The present invention was completed based on this finding that it has an excellent skin-whitening effect when it is incorporated into an external preparation base at a certain concentration or more.
【０００９】すなわち、本発明は化１、化２の一般式で
表されるカフェイン酸配糖体、例えばカフェイン酸３−
β−Ｄ−グルコシド、カフェイン酸４−β−Ｄ−グルコ
シドを含有することを特徴とする皮膚外用剤であり、好
ましい様態としては、カフェイン酸配糖体の含有量が、
外用剤全量に対し０．１〜１０重量％であることを特徴
とする皮膚外用剤である。That is, the present invention provides a caffeic acid glycoside represented by the general formula of Chemical Formula 1 or Chemical Formula 2, for example, caffeic acid 3-
β-D-glucoside, caffeic acid 4-β-D-glucoside is a skin external preparation characterized by containing, as a preferred mode, the content of caffeic acid glycoside,
The external preparation for skin is characterized by being 0.1 to 10% by weight based on the total amount of the external preparation.
【００１０】更に好ましい様態としては、紫外線防御
剤、創傷治癒剤、新陳代謝促進剤、抗炎症剤、保湿剤の
うち少なくとも一種以上を併用することを特徴とする皮
膚外用剤である。A more preferable mode is a skin external preparation characterized by using at least one or more of an ultraviolet protective agent, a wound healing agent, a metabolism promoting agent, an anti-inflammatory agent and a moisturizing agent.
【００１１】以下、本発明を詳細に述べる。 ＜１＞本発明に用いるカフェイン酸配糖体 本発明に適用されるカフェイン酸配糖体とは、カフェイ
ン酸の２つの水酸基の一方に、Ｌ−アラビノース、Ｌ−
キシロース、Ｄ−リボース、Ｌ−リキソース等の５炭糖
の残基、Ｄ−グルコース、Ｄ−ガラクトース、Ｌ−ガラ
クトース、Ｄ−マンノース、Ｄ−タロース、Ｄ−フルク
トース等の６炭糖の残基、Ｄ−グルコサミン、Ｄ−ガラ
クトサミン、シアル酸等のアミノ糖の残基、Ｄ−グルク
ロン酸、Ｄ−ガラクツロン酸、Ｄ−マンヌロン酸等のウ
ロン酸の残基が結合したものであり、美白効果、入手の
容易さ、安定性、安全性の面から特に、Ｄ−グルコース
残基が結合したものが好ましい。例えば、カフェイン酸
３−β−Ｄ−グルコシド、カフェイン酸４−β−Ｄ−グ
ルコシドを例示することができるが、これらに限定され
るものではない。The present invention will be described in detail below. <1> Caffeic Acid Glycosides Used in the Present Invention Caffeic acid glycosides used in the present invention mean that one of the two hydroxyl groups of caffeic acid has L-arabinose or L-.
Xylose, D-ribose, L-lyxose and other 5-carbon sugar residues, D-glucose, D-galactose, L-galactose, D-mannose, D-talose, D-fructose and other 6-carbon sugar residues, A residue of an amino sugar such as D-glucosamine, D-galactosamine, and sialic acid, and a residue of uronic acid such as D-glucuronic acid, D-galacturonic acid, and D-mannuronic acid are bound to each other. From the viewpoints of easiness, stability, and safety, those having a D-glucose residue bonded thereto are preferable. For example, caffeic acid 3-β-D-glucoside and caffeic acid 4-β-D-glucoside can be exemplified, but the invention is not limited thereto.
【００１２】カフェイン酸３−β−Ｄ−グルコシドは、
ジャガイモ（Solanum tuberosum）、ヨーロッパクロヤ
マナラシ（Populus nigra）、トマト（Lycopersicum es
culentum）等に含有することが知られている物質であ
り、またカフェイン酸４−β−Ｄ−グルコシドは、クラ
ンベリー（Vaccinnum macrocarpon）、トマト（Lycoper
sicum esculentum）等に含有することが知られている物
質である。Caffeic acid 3-β-D-glucoside is
Potato (Solanum tuberosum), European Pope (Populus nigra), Tomato (Lycopersicum es)
culentum) and caffeic acid 4-β-D-glucoside are known to be contained in cranberry (Vaccinnum macrocarpon), tomato (Lycoper).
It is a substance known to be contained in sicum esculentum).
【００１３】これらの原料からカフェイン酸配糖体を得
る方法としては、ハーボーンら(Harborne J. B. & Corn
er J. Biochem. J. 81, 242-250, 1961)、及びウィンタ
ーら（Winter M. & Herrmann K. Journal of Chromatog
raphy, 315, 243-251 1984)の方法が挙げられる。As a method for obtaining caffeic acid glycosides from these raw materials, Harborne JB & Corn
er J. Biochem. J. 81 , 242-250, 1961), and Winter et al. (Winter M. & Herrmann K. Journal of Chromatog.
Raphy, 315 , 243-251 1984).
【００１４】以下に、カフェイン酸３−β−Ｄ−グルコ
シドを例として入手法を示す。ジャガイモを破砕後、エ
タノールで７日間室温抽出し、得られた抽出液をエバポ
レーターを用いて溶媒留去した後、真空ポンプで濃縮乾
固し、濃縮物を得た。The method for obtaining caffeic acid 3-β-D-glucoside will be described below as an example. After crushing the potatoes, the mixture was extracted with ethanol for 7 days at room temperature, the obtained extract was distilled off the solvent using an evaporator, and then concentrated to dryness with a vacuum pump to obtain a concentrate.
【００１５】次に、この濃縮物をポリアミドカラムにの
せ、水にて溶出した後、更にメタノールにて溶出した。
メタノールにて溶出した画分をエバポレーターにて濃縮
し、この濃縮物を逆相シリカゲルカラムを用いた分取Ｈ
ＰＬＣにて精製し、カフェイン酸３−β−Ｄ−グルコシ
ドを得た。精製物は、ＮＭＲにて確認した。Next, this concentrate was placed on a polyamide column, eluted with water, and then eluted with methanol.
Fractions eluted with methanol were concentrated with an evaporator, and the concentrate was collected using a reverse phase silica gel column.
Purification by PLC gave caffeic acid 3-β-D-glucoside. The purified product was confirmed by NMR.
【００１６】尚、カフェイン酸３−β−Ｄ−グルコシド
は、化学的、または酵素的合成によっても得ることがで
き、本発明に用いることができる。本発明に用いられる
カフェイン酸配糖体の配合割合は、外用剤全量に対し
０．１〜１０重量％が好ましい。Caffeic acid 3-β-D-glucoside can be obtained by chemical or enzymatic synthesis and can be used in the present invention. The compounding ratio of the caffeic acid glycoside used in the present invention is preferably 0.1 to 10% by weight with respect to the total amount of the external preparation.
【００１７】すなわち、日焼けによるシミ・ソバカス、
色黒を予防することを目的とした化粧料の如き皮膚外用
剤に用いる場合は０．１重量％以上が、また色素沈着症
の治療を目的とする薬剤として外用剤に用いる場合は１
重量％以上が有効量として使用できるものである。使用
量が０．１重量％未満では本発明の目的を達し得ず、ま
た１０重量％を大幅に越えると本発明の効果が頭打ちに
なるので上記範囲で配合することが好ましい。That is, spots and freckles caused by sunburn,
0.1% by weight or more when used as an external preparation for skin such as cosmetics for the purpose of preventing darkening, and 1 when used as an external preparation as a drug for treating pigmentation.
Weight percent or more can be used as an effective amount. If the amount used is less than 0.1% by weight, the object of the present invention cannot be achieved, and if it exceeds 10% by weight, the effect of the present invention reaches the ceiling.
【００１８】＜２＞本発明に用いる併用成分 皮膚外用剤に、紫外線防御剤、創傷治癒剤、新陳代謝促
進剤、抗炎症剤、保湿材のうち少なくとも一種を上記カ
フェイン酸配糖体と併用して配合することにより、さら
に皮膚色素沈着症の改善・治療効果を高めることが期待
される。<2> Concomitant component used in the present invention A skin external preparation is used in combination with at least one of an ultraviolet protective agent, a wound healing agent, a metabolism promoting agent, an anti-inflammatory agent, and a moisturizing agent in combination with the above caffeic acid glycoside. It is expected that the effect of ameliorating and / or treating skin pigmentation disease can be further enhanced by blending the above.
【００１９】以下に、これらの併用成分について説明す
る。紫外線防御剤とは、アスコルビン酸またはその誘導
体、イソフェルラ酸またはその塩、グルタチオンまたは
その誘導体、オキシベンゾンまたはその誘導体、ｐ−ア
ミノ安息香酸またはその誘導体、ウロカニン酸またはそ
の誘導体、コウジ酸、酸化チタン等から選ばれる一種ま
たは二種以上である。The components used in combination will be described below. UV protectors include ascorbic acid or its derivatives, isoferulic acid or its salts, glutathione or its derivatives, oxybenzone or its derivatives, p-aminobenzoic acid or its derivatives, urocanic acid or its derivatives, kojic acid, titanium oxide, etc. One or more selected.
【００２０】創傷治癒剤とは、当帰エキス、アラントイ
ンまたはその誘導体、ローズマリー抽出物等から選ばれ
る一種または二種以上である。新陳代謝促進剤とは、胎
盤抽出物（水溶性プラセンタエキス）、γ−オリザノー
ル、各種アミノ酸、ビタミンＥまたはその誘導体などか
ら選ばれる一種または二種以上である。The wound healing agent is one or more selected from toki extract, allantoin or its derivative, rosemary extract and the like. The metabolic stimulant is one or more selected from placenta extract (water-soluble placenta extract), γ-oryzanol, various amino acids, vitamin E or its derivatives and the like.
【００２１】抗炎症剤とは、グリチルレチン酸またはそ
の誘導体、グリチルリチン酸またはその誘導体、ビサボ
ロール、ゲラニイン、マロニエ抽出物、アロエ抽出物等
から選ばれる一種または二種以上である。The anti-inflammatory agent is one or more selected from glycyrrhetinic acid or its derivative, glycyrrhizic acid or its derivative, bisabolol, geraniin, horse chestnut extract, aloe extract and the like.
【００２２】保湿剤とは、ヒアルロン酸またはその塩、
スフィンゴ糖脂質、コラーゲン、エラスチン、ムチン、
ソウハクヒ、ローヤルゼリー、カゼインナトリウム、レ
シチン、キチンやキトサンまたはそれらの誘導体等から
選ばれる一種または二種以上である。Moisturizers are hyaluronic acid or salts thereof,
Glycosphingolipid, collagen, elastin, mucin,
It is one or more selected from sohakuhi, royal jelly, sodium caseinate, lecithin, chitin, chitosan and their derivatives.
【００２３】＜３＞本発明の皮膚外用剤 本発明の皮膚外用剤とは、例えば軟膏、クリーム、乳
液、ローション、パック、浴用剤等、従来皮膚外用剤に
用いるものであればいずれでもよく、剤型は特に問わな
い。<3> Skin external preparation of the present invention The skin external preparation of the present invention may be any ointment, cream, emulsion, lotion, pack, bath agent or the like as long as it is a conventional external preparation for skin. The dosage form is not particularly limited.
【００２４】また、本発明の皮膚外用剤には前述のカフ
ェイン酸配糖体あるいは紫外線防御剤、創傷治癒剤、新
陳代謝促進剤、抗炎症剤、保湿材の他に、医薬品、化粧
品などに一般に用いられる各種成分、すなわち水性成
分、油性成分、粉末成分、界面活性剤、増粘剤、色剤、
香料、防腐剤、或は抗酸化剤、キレート剤、胸線エキ
ス、ホルモン類、核酸類、各種ビタミン、カフェイン酸
配糖体以外の他の美白成分などを配合することができ
る。In addition to the caffeic acid glycoside or the ultraviolet protective agent, the wound healing agent, the metabolism promoting agent, the anti-inflammatory agent and the moisturizing agent, the external preparation for skin of the present invention is generally used in pharmaceuticals, cosmetics and the like. Various components used, namely, aqueous component, oil component, powder component, surfactant, thickener, colorant,
A fragrance, an antiseptic, or an antioxidant, a chelating agent, a chest line extract, hormones, nucleic acids, various vitamins, and whitening ingredients other than caffeic acid glycosides can be added.
【００２５】 ＜４＞本発明に用いるカフェイン酸配糖体の効果 次に、本発明に使用されるカフェイン酸配糖体の作用を
明らかにするために、メラニン抑制効果について、カフ
ェイン酸３−β−Ｄ−グルコシドを例としてテストし
た。<4> Effect of Caffeic Acid Glycosides Used in the Present Invention Next, in order to clarify the action of the caffeic acid glycosides used in the present invention, regarding the melanin suppressing effect, caffeic acid 3-β-D-glucoside was tested as an example.
【００２６】プラスチック培養フラスコ（７５ｃｍ2）
に３×１０4個のマウスメラノーマ由来細胞Ｂ−１６を
はん種し、１０％牛胎児血清を含むイーグルＭＥＭ培地
１０ｍｌで、５％二酸化炭素条件下で３７℃で培養し
た。２日後カフェイン酸３−β−Ｄ−グルコシドをそれ
ぞれ培地中の濃度で１×１０-6〜１×１０-2％（ｗ／
ｖ）となるように添加した。Plastic culture flask (75 cm 2 )
3 × 10 4 mouse melanoma-derived cells B-16 were seeded and cultured in 10 ml of Eagle's MEM medium containing 10% fetal bovine serum at 37 ° C. under 5% carbon dioxide conditions. Two days later, caffeic acid 3-β-D-glucoside was added to the medium at a concentration of 1 × 10 −6 to 1 × 10 −2 % (w /
v) was added.
【００２７】５日後、１０％牛胎児血清を含むイーグル
ＭＥＭ培地１５ｍｌ及び１×１０-6〜１×１０-2％（ｗ
／ｖ）のカフェイン酸３−β−Ｄ−グルコシドを添加
し、さらに２日間培養した。培養後培地を除去し、細胞
をリン酸緩衝液で洗浄した後、トリプシン及びＥＤＴＡ
含有溶液を使用して細胞を培養フラスコから剥離させ
た。After 5 days, 15 ml of Eagle's MEM medium containing 10% fetal bovine serum and 1 × 10 −6 to 1 × 10 −2 % (w)
/ V) Caffeic acid 3-β-D-glucoside was added, and the mixture was further cultured for 2 days. After culturing, the medium was removed, the cells were washed with phosphate buffer, and then trypsin and EDTA were added.
The cells were detached from the culture flask using the containing solution.
【００２８】この細胞懸濁液から遠心分離により回収し
た細胞をリン酸緩衝液で洗浄した後、沈渣に１Ｎ水酸化
ナトリウム水溶液を加えて加熱溶解した。冷却後、クロ
ロホルムを加えて、再び遠心分離した。これによって得
られた上清の４００ｎｍにおける吸光度を測定し、あら
かじめ合成メラニンを用いて作製しておいた検量線より
メラニン量を求めた。尚、メラニン量は１０6個細胞当
りの量として求め、結果を表１に示した。The cells recovered from this cell suspension by centrifugation were washed with a phosphate buffer, and the precipitate was dissolved by heating with a 1N aqueous sodium hydroxide solution. After cooling, chloroform was added and the mixture was centrifuged again. The absorbance at 400 nm of the supernatant thus obtained was measured, and the amount of melanin was determined from a calibration curve prepared in advance using synthetic melanin. The amount of melanin was determined as the amount per 10 6 cells, and the results are shown in Table 1.
【００２９】[0029]
【表１】 [Table 1]
【００３０】この結果から明らかなように、カフェイン
酸３−β−Ｄ−グルコシドは色素細胞内のメラニン生成
に対し顕著な抑制効果を示すことが実証された。As is apparent from these results, it was demonstrated that caffeic acid 3-β-D-glucoside has a remarkable inhibitory effect on melanin production in pigment cells.
【００３１】[0031]
【実施例】以下に本発明の実施例を示すが、本発明はこ
れに制限されるものではない。尚、配合割合は重量部で
ある。EXAMPLES Examples of the present invention will be shown below, but the present invention is not limited thereto. The mixing ratio is parts by weight.
【００３２】[0032]
【実施例１〜３】本発明の皮膚外用剤として、カフェイ
ン酸配糖体を配合したクリームを説明する。 （製法）表２Ａ、Ｂの各成分を各々混合し、８０℃に加
熱した。Ａの全成分をＢの全成分に加えて攪拌乳化し、
その後冷却してクリームを得た。対照として、比較例１
〜３のクリームを同様に製造した。Examples 1 to 3 As the external preparation for skin of the present invention, a cream containing caffeic acid glycoside will be described. (Production method) The components shown in Tables 2A and 2B were mixed and heated to 80 ° C. Add all components of A to all components of B, emulsify with stirring,
Then, it was cooled to obtain a cream. Comparative Example 1 as a control
~ 3 creams were similarly prepared.
【００３３】[0033]
【表２】 [Table 2]
【００３４】[0034]
【実施例４〜６】次に、本発明の皮膚外用剤として、紫
外線防御剤としてＬ−アスコルビン酸リン酸エステルマ
グネシウム塩、創傷治療剤として当帰エキス、新陳代謝
促進剤として胎盤抽出物をカフェイン酸配糖体と併用し
て配合したクリームについて説明する。Examples 4 to 6 Next, as a skin external preparation of the present invention, L-ascorbyl phosphate magnesium salt as an ultraviolet protection agent, Toki extract as a wound healing agent, and placenta extract as a metabolism promoter are caffeine. The cream blended together with the acid glycoside will be described.
【００３５】（製法）表３Ａ、Ｂの各成分を各々混合
し、８０℃に加熱した。Ａの全成分をＢの全成分に加え
て攪拌乳化し、その後冷却して実施例４〜６のクリーム
を得た。同様に、比較４〜６のクリームを製造した。(Production method) The components shown in Tables 3A and 3B were mixed and heated to 80 ° C. All the ingredients of A were added to all the ingredients of B, emulsified with stirring, and then cooled to obtain the creams of Examples 4 to 6. Similarly, the creams of comparisons 4-6 were prepared.
【００３６】[0036]
【表３】 [Table 3]
【００３７】[0037]
【実施例７、８】さらに、本発明の皮膚外用剤として、
抗炎症剤としてグリチルレチン酸ステアリル、保湿剤と
してヒアルロン酸をカフェイン酸配糖体と併用して配合
したクリームについて説明する。[Examples 7 and 8] Further, as a skin external preparation of the present invention,
A cream containing stearyl glycyrrhetinate as an anti-inflammatory agent and hyaluronic acid as a moisturizer in combination with caffeic acid glycoside will be described.
【００３８】（製法）表４Ａ、Ｂの各成分を各々混合
し、８０℃に加熱した。Ａの全成分をＢの全成分に加え
て攪拌乳化し、その後冷却して実施例７、８のクリーム
を得た。同様に比較例７、８のクリームを製造した。(Production method) The components shown in Tables 4A and 4B were mixed and heated to 80 ° C. All the components of A were added to all the components of B to emulsify with stirring, and then cooled to obtain the creams of Examples 7 and 8. Similarly, the creams of Comparative Examples 7 and 8 were produced.
【００３９】[0039]
【表４】 [Table 4]
【００４０】[0040]
【実施例９】本発明の皮膚外用剤として、カフェイン酸
配糖体及び新陳代謝促進剤として胎盤抽出物を配合した
乳液について説明する。 （製法）表５Ａ、Ｂの成分を７０℃で各々攪はんしなが
ら溶解した。Ｂの成分にＡの成分を加えて予備乳化を行
い、ホモミキサーで均一に乳化し、乳化後かき混ぜなが
ら３０℃まで冷却して実施例９の乳液を得た。Example 9 As an external preparation for skin of the present invention, an emulsion containing caffeic acid glycoside and a placenta extract as a metabolism promoter will be described. (Production method) The components shown in Tables 5A and 5B were dissolved at 70 ° C with stirring. The component A was added to the component B to carry out preliminary emulsification, and the mixture was uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. with stirring to obtain an emulsion of Example 9.
【００４１】[0041]
【表５】 [Table 5]
【００４２】[0042]
【実施例１０】次に、実施例として、カフェイン酸３−
Ｄ−グルコサミドを配合した化粧水を説明する。 （製法）表６Ａの各成分を合わせ、室温下で溶解した。
一方、Ｂの各成分も室温下で溶解し、これをＡの溶解物
に加えて可溶化し、化粧水を得た。Example 10 Next, as an example, caffeic acid 3-
A lotion containing D-glucosamide will be described. (Manufacturing method) The components shown in Table 6A were combined and dissolved at room temperature.
On the other hand, each component of B was also dissolved at room temperature, and this was added to the dissolved product of A to solubilize it to obtain a lotion.
【００４３】[0043]
【表６】 [Table 6]
【００４４】[0044]
【実施例１１】 （製法）表７Ａ及びＢの各成分を７０℃で各々攪はんし
ながら溶解した後、Ａの成分にＢの成分を加えて乳化し
た後、３０℃まで冷却して軟膏を得た。[Example 11] (Production method) Each of the ingredients shown in Table 7A and B was dissolved at 70 ° C with stirring, and the ingredient B was added to the ingredient A to emulsify the mixture. Got
【００４５】[0045]
【表７】 [Table 7]
【００４６】＜評価＞以下に、本発明の皮膚外用剤の安
定性、安全性（皮膚累積刺激性、接触感作性）、色素沈
着改善効果について説明する。 （安定性）カフェイン酸３−β−Ｄ−グルコシド溶液、
及びこれを配合した実施例１のクリームの安定性をテス
トした。<Evaluation> The stability, safety (cumulative skin irritation, contact sensitization) and pigmentation improving effect of the external preparation for skin of the present invention will be described below. (Stability) 3-β-D-glucoside caffeic acid solution,
And the stability of the cream of Example 1 containing the same was tested.
【００４７】０．１Ｎ水酸化ナトリウム水溶液を用い
て、０．１重量％のカフェイン酸３−β−Ｄ−グルコシ
ド溶液及び対照品としてカフェイン酸溶液を調製した。
これらの溶液を実施例１のクリームと共に、３７℃で３
カ月保存した後、肉眼にて着色度を評価した。A 0.1% by weight caffeic acid 3-β-D-glucoside solution and a caffeic acid solution as a control were prepared using a 0.1N sodium hydroxide aqueous solution.
These solutions were combined with the cream of Example 1 at 37 ° C for 3 hours.
After storing for a month, the degree of coloring was evaluated with the naked eye.
【００４８】安定性の評価は表８に示した着色度の評点
に従って行い、結果を表９に示した。The stability was evaluated according to the coloring degree ratings shown in Table 8, and the results are shown in Table 9.
【００４９】[0049]
【表８】 [Table 8]
【００５０】[0050]
【表９】 [Table 9]
【００５１】この結果から明らかなように、カフェイン
酸３−β−Ｄ−グルコシドはカフェイン酸に比べ安定で
ある。また本発明の皮膚外用剤（実施例１のクリーム）
も安定であることがわかる。As is clear from this result, caffeic acid 3-β-D-glucoside is more stable than caffeic acid. Further, the external preparation for skin of the present invention (cream of Example 1)
It turns out that is also stable.
【００５２】（安全性）次に、カフェイン酸３−β−Ｄ
−グルコシド、カフェイン酸及びこれを配合した皮膚外
用剤の安全性をテストした。安全性の指標として皮膚累
積刺激性、接触感作性について評価した。 １．皮膚累積刺激性 皮膚に累積使用した場合の皮膚に対する刺激性について
調べた。(Safety) Next, caffeic acid 3-β-D
-The safety of glucoside, caffeic acid and external preparations for skin containing the same was tested. Cumulative skin irritation and contact sensitization were evaluated as indicators of safety. 1. Cumulative skin irritation The cumulative irritation to the skin was investigated.
【００５３】白色モルモット（各群５匹）の背部を電気
バリカンを用いて除毛し、消毒液で洗浄した。この部位
の皮膚にカフェイン酸３−β−Ｄ−グルコシド、カフェ
イン酸の１％、５％、１０％エタノール：水（１：１）
溶液、あるいは実施例１のクリームを、１日１回５０ｍ
ｇ／ｃｍ2塗布し、刺激の度合を毎日肉眼測定した。紅
斑、浮腫の出現した個体の数を表１０に示した。The back of white guinea pigs (five in each group) was shaved with an electric clipper and washed with an antiseptic solution. Caffeic acid 3-β-D-glucoside, caffeic acid 1%, 5%, 10% ethanol: water (1: 1)
50m of the solution or the cream of Example 1 once a day
g / cm 2 was applied, and the degree of irritation was visually measured daily. Table 10 shows the number of individuals in which erythema and edema appeared.
【００５４】[0054]
【表１０】 [Table 10]
【００５５】この結果から明らかなように、カフェイン
酸は５％、１０％の濃度で刺激が出るのに対し、カフェ
イン酸３−β−Ｄ−グルコシドはいずれの濃度でも皮膚
刺激性がなく安全であることがわかる。As is clear from these results, caffeic acid is irritating at a concentration of 5% and 10%, whereas caffeic acid 3-β-D-glucoside has no skin irritation at any concentration. Turns out to be safe.
【００５６】２．接触感作性 次に、皮膚に対する接触感作性について調べた。2. Contact Sensitization Next, contact sensitization to the skin was examined.
【００５７】体重３８０〜４２０ｇの健常なモルモット
（各群５匹）を使用し、佐藤らの方法（Contact Dermat
osis，７，２２５（１９８１）を参照）準じて行った。
刈毛したモルモット頸部の２×４ｃｍの４隅に、フロイ
ント・コンプリート・アジュバントと等量の蒸留水との
乳化液０．１ｍｌを皮内注射し、注射部位の角質層に井
型の傷をつけた後、０．５％カフェイン酸３−β−Ｄ−
グルコシド溶液、０．５％カフェイン酸溶液あるいは実
施例１のクリーム各０．１ｍｌを塗布した絆創膏を貼布
し、２４時間放置した。この操作をその後２日間続け
た。Healthy guinea pigs weighing 380 to 420 g (5 animals in each group) were used and the method of Sato et al. (Contact Dermat) was used.
osis, 7 , 225 (1981)).
An intradermal injection of 0.1 ml of an emulsified solution of Freund's complete adjuvant and an equivalent amount of distilled water was made into 4 corners of 2 × 4 cm of the shaved guinea pig neck, and a well-shaped wound was formed on the stratum corneum of the injection site. After applying, 0.5% caffeic acid 3-β-D-
A glucoside solution, a 0.5% caffeic acid solution, or a plaster coated with 0.1 ml each of the cream of Example 1 was applied and left for 24 hours. This operation was continued for 2 days thereafter.
【００５８】７日目に、剃毛した肩甲骨上にラウリル硫
酸ナトリウム１０％を含むワセリンを塗布し、２４時間
後に上記各物質溶液０．２ｍｌを２×４ｃｍの濾紙を用
いて４８時間閉塞適用した。On the 7th day, vaseline containing 10% of sodium lauryl sulfate was applied on the shaved scapula, and after 24 hours, 0.2 ml of each substance solution was occluded for 48 hours using a 2 × 4 cm filter paper. did.
【００５９】感作誘導操作開始２１日目に、剃毛した背
部皮膚に、段階希釈した上記各物質溶液を塗布し、解放
適用した。感作操作終了後、４８時間目に皮膚反応（紅
斑及び浮腫）を観察した。On the 21st day from the start of the sensitization induction operation, the shaved dorsal skin was applied with the serially diluted solution of each of the above substances, and then applied openly. Skin reactions (erythema and edema) were observed 48 hours after the completion of the sensitization operation.
【００６０】その結果、カフェイン酸では、１匹に中程
度の紅斑が認められたが、カフェイン酸３−β−Ｄ−グ
ルコシド及び実施例１のクリームでは、いずれのモルモ
ットにおいても紅斑、浮腫はまったく観察されず、感作
性は認められなかった。 （色素沈着改善効果）次に、カフェイン酸３−β−Ｄ−
グルコシドを配合した皮膚外用剤の色素沈着改善効果
を、実使用テストによって評価した。As a result, caffeic acid showed moderate erythema in one animal, but caffeic acid 3-β-D-glucoside and the cream of Example 1 produced erythema and edema in all guinea pigs. Was not observed at all and no sensitization was observed. (Pigmentation improving effect) Next, caffeic acid 3-β-D-
The pigmentation improving effect of the external preparation for skin containing glucoside was evaluated by a practical use test.
【００６１】色黒、シミ、ソバカスに悩む女性ボランテ
ィア８０名を、色素沈着がほぼ同程度な８群に分け、カ
フェイン酸３−β−Ｄ−グルコシドを配合した実施例１
〜４のクリームあるいは対照品として比較例１〜４のク
リームを、各々３カ月間連用してもらった。Eighty female volunteers suffering from dark blacks, spots, and freckles were divided into eight groups with almost the same pigmentation, and caffeic acid 3-β-D-glucoside was added to Example 1.
The creams of Comparative Examples 1 to 4 or the creams of Comparative Examples 1 to 4 were continuously used for 3 months.
【００６２】３カ月後、美容専門家５名により、色黒、
シミ、ソバカスについての改善効果の程度を評価した。
「やや改善」〜「著しく改善」に相当する人数の全体に
対する割合を有効性として、結果を表１１に示した。After 3 months, 5 beauty specialists gave
The degree of improvement effect on spots and freckles was evaluated.
The results are shown in Table 11, with the ratio of the number of people corresponding to "slightly improved" to "remarkably improved" to the whole being taken as effectiveness.
【００６３】[0063]
【表１１】 [Table 11]
【００６４】この結果から明らかなように、カフェイン
酸３−β−Ｄ−グルコシドを皮膚外用剤全量に対し０．
１〜１０重量％配合することにより、優れた色素沈着改
善効果を発揮することが認められた。As is clear from this result, caffeic acid 3-β-D-glucoside was added to the total amount of the external preparation for skin at 0.
It was confirmed that an excellent pigmentation-improving effect was exhibited by adding 1 to 10% by weight.
【００６５】また、試験期間中にいずれのクリームにお
いてもなんら副作用は観察されず、本発明品は皮膚に対
して安全であることが確認された。以上示したように、
本発明の皮膚外用剤は、安定性、安全性、色素沈着改善
効果に優れている。No side effects were observed in any of the creams during the test period, confirming that the product of the present invention is safe for the skin. As shown above,
The external preparation for skin of the present invention is excellent in stability, safety and pigmentation improving effect.
【００６６】[0066]
【発明の効果】本発明によれば、カフェイン酸配糖体を
含有する皮膚外用剤に、メラニン抑制効果が顕著であ
り、しかも安定性に優れ、皮膚累積刺激性や接触感作性
も低く、皮膚色素沈着症の予防、改善に対して優れた効
果を発揮する。INDUSTRIAL APPLICABILITY According to the present invention, an external preparation for skin containing caffeic acid glycoside has a remarkable melanin-suppressing effect, is excellent in stability, and has low skin cumulative irritation and contact sensitization. , Exerts an excellent effect on prevention and improvement of skin pigmentation.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 片桐 崇行 神奈川県横浜市神奈川区高島台27番地１ポ ーラ化成工業株式会社横浜研究所内 (72)発明者 大貫 敬子 神奈川県横浜市神奈川区高島台27番地１ポ ーラ化成工業株式会社横浜研究所内 (72)発明者 中野 博行 神奈川県横浜市神奈川区高島台27番地１ポ ーラ化成工業株式会社横浜研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Takayuki Katagiri, Inventor Takayukidai, Takashimadai, Kanagawa-ku, Yokohama, Kanagawa 1 Polar Chemical Industry Co., Ltd. Yokohama Research Laboratory (72) Keiko Onuki Takashimadai, Kanagawa-ku, Yokohama, Kanagawa 27, 1 Polar Chemical Industry, Yokohama Laboratory (72) Inventor Hiroyuki Nakano Takashimadai, Kanagawa-ku, Kanagawa Prefecture 27, 1 Polar Chemical Industry, Yokohama Laboratory
Claims (4)
体を含有することを特徴とする皮膚外用剤。 【化１】 【化２】 式中、Ｒは５炭糖残基、６炭糖残基、アミノ糖残基、ウ
ロン酸残基を表す。）1. An external preparation for skin comprising a caffeic acid glycoside represented by the following general formula. [Chemical 1] [Chemical 2] In the formula, R represents a 5-carbon sugar residue, a 6-carbon sugar residue, an amino sugar residue, or a uronic acid residue. )
酸３−β−Ｄ−グルコシド、カフェイン酸４−β−Ｄ−
グルコシドの少なくとも一方を含むことを特徴とする請
求項１記載の皮膚外用剤。2. The caffeic acid glycoside comprises caffeic acid 3-β-D-glucoside and caffeic acid 4-β-D-.
The external preparation for skin according to claim 1, which contains at least one of glucosides.
用剤全量に対し０．１〜１０重量％であることを特徴と
する請求項１又は２に記載の皮膚外用剤。3. The external preparation for skin according to claim 1, wherein the content of the caffeic acid glycoside is 0.1 to 10% by weight based on the total amount of the external preparation.
進剤、抗炎症剤、保湿材のうち少なくとも一種を併用す
ることを特徴とする請求項１〜３のいずれか１項に記載
の皮膚外用剤。4. The external skin application according to any one of claims 1 to 3, wherein at least one of an ultraviolet protective agent, a wound healing agent, a metabolism promoting agent, an anti-inflammatory agent and a moisturizing agent is used in combination. Agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4015553A JP2997358B2 (en) | 1992-01-30 | 1992-01-30 | External preparation for skin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4015553A JP2997358B2 (en) | 1992-01-30 | 1992-01-30 | External preparation for skin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05201846A true JPH05201846A (en) | 1993-08-10 |
| JP2997358B2 JP2997358B2 (en) | 2000-01-11 |
Family
ID=11891963
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4015553A Expired - Fee Related JP2997358B2 (en) | 1992-01-30 | 1992-01-30 | External preparation for skin |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2997358B2 (en) |
Cited By (12)
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|---|---|---|---|---|
| WO1995024896A3 (en) * | 1994-03-15 | 1995-11-09 | Unilever Plc | Use of antagonists of egf or tgf-alpha for the treatment and prophylaxis of acne |
| WO1995029681A1 (en) * | 1994-04-29 | 1995-11-09 | Texas Biotechnology Corporation | COMPOSITIONS AND METHODS FOR INHIBITING THE BINDING OF E-SELECTIN OR P-SELECTIN TO SIALYL-LEWISx OR SIALYL-LEWIS?a¿ |
| JPH10147514A (en) * | 1996-11-19 | 1998-06-02 | Pola Chem Ind Inc | Cosmetic |
| JP2003238585A (en) * | 2002-02-08 | 2003-08-27 | Ogawa & Co Ltd | Naphthol glycoside and bleaching composition for external use containing the same |
| JP2004123563A (en) * | 2002-09-30 | 2004-04-22 | Iskra Ind Co Ltd | Cosmetic containing fruit oil obtained from hippophae and ingredients extracted from other galenicals |
| JP2004315386A (en) * | 2003-04-14 | 2004-11-11 | Hayashibara Takeshi | Anti-microbial agent |
| JP2007519722A (en) * | 2004-01-30 | 2007-07-19 | アクセス ビジネス グループ インターナショナル エルエルシー | Overall composition and method for reducing skin pigmentation |
| JP2008214272A (en) * | 2007-03-05 | 2008-09-18 | Oriza Yuka Kk | Skin-lightening agent |
| US20110212913A1 (en) * | 2008-10-31 | 2011-09-01 | Provexis Natural Products Limited | Therapeutic compositions comprising phenolic acids for treating conditions related to inappropriate platelet aggregation |
| US10813968B2 (en) | 2012-12-24 | 2020-10-27 | Provexis Natural Products Limited | Method of treating a human suffering from post exercise muscle soreness |
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1992
- 1992-01-30 JP JP4015553A patent/JP2997358B2/en not_active Expired - Fee Related
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995024896A3 (en) * | 1994-03-15 | 1995-11-09 | Unilever Plc | Use of antagonists of egf or tgf-alpha for the treatment and prophylaxis of acne |
| WO1995029681A1 (en) * | 1994-04-29 | 1995-11-09 | Texas Biotechnology Corporation | COMPOSITIONS AND METHODS FOR INHIBITING THE BINDING OF E-SELECTIN OR P-SELECTIN TO SIALYL-LEWISx OR SIALYL-LEWIS?a¿ |
| JPH10147514A (en) * | 1996-11-19 | 1998-06-02 | Pola Chem Ind Inc | Cosmetic |
| JP2003238585A (en) * | 2002-02-08 | 2003-08-27 | Ogawa & Co Ltd | Naphthol glycoside and bleaching composition for external use containing the same |
| JP2004123563A (en) * | 2002-09-30 | 2004-04-22 | Iskra Ind Co Ltd | Cosmetic containing fruit oil obtained from hippophae and ingredients extracted from other galenicals |
| JP2004315386A (en) * | 2003-04-14 | 2004-11-11 | Hayashibara Takeshi | Anti-microbial agent |
| JP2007519722A (en) * | 2004-01-30 | 2007-07-19 | アクセス ビジネス グループ インターナショナル エルエルシー | Overall composition and method for reducing skin pigmentation |
| JP2008214272A (en) * | 2007-03-05 | 2008-09-18 | Oriza Yuka Kk | Skin-lightening agent |
| US20110212913A1 (en) * | 2008-10-31 | 2011-09-01 | Provexis Natural Products Limited | Therapeutic compositions comprising phenolic acids for treating conditions related to inappropriate platelet aggregation |
| US10864241B2 (en) | 2012-04-23 | 2020-12-15 | Provexis Natural Products Limited | Use of tomato extract as antihypertensive agent and process for making water soluble sugar free tomato extract |
| US10813968B2 (en) | 2012-12-24 | 2020-10-27 | Provexis Natural Products Limited | Method of treating a human suffering from post exercise muscle soreness |
| US10905733B2 (en) | 2016-11-02 | 2021-02-02 | Provexis Natural Products Limited | Water soluble tomato extract protects against adverse effects of air pollution |
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|---|---|
| JP2997358B2 (en) | 2000-01-11 |
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