TW201242607A

TW201242607A - Whitening agent

Info

Publication number: TW201242607A
Application number: TW101126922A
Authority: TW
Inventors: Yoshihide Suwa; Kenji Oguchi; Yoshinori Nozawa; Yukihiro Akao
Original assignee: Suntory Holdings Ltd
Priority date: 2004-01-30
Filing date: 2005-01-27
Publication date: 2012-11-01
Also published as: JP2011236238A; WO2005072756A1; TWI527588B; JP4810230B2; CN100506206C; TWI415618B; CN1913908A; JPWO2005072756A1; TW200528126A

Abstract

The present invention provides a whitening agent that can be acquired from natural sources, which having high safety for human bodies, without issues of stable supply, and having satisfactory patient compliance, characterized by comprising a solvent extract from a plant of the oaks which belongs to Quercus species of the Fagaceae family.

Description

201242607 六、發明說明：【發明所屬之技術領域】本發明乃關於美白劑。更詳言之，本發曰月殼斗科櫟屬植物之溶劑萃取物而具有美白乃關於含有 1下用之飲+ σ 香粧品或醫藥品。双、【先前技術】老人斑、雀斑及日曬後皮膚上之色素洗凝現年齡之增加，容易發生、增加或不易消失而，隨著層者之須惱。為皮膚著色之卵之黑色中高年齡 % 由在表古；5直皮間之黑細胞（melanocyte)中之黑色素 (melanasome)產生’所產生之黑色素藉浓祿二成顆本乍用擴散到鄰近細胞。該黑細胞内之生化學反應被推夠如下、需胺基酸之酪胺酸受酪胺酸激酶之作用而成為夕卩為必藉酵素或非酵素性氧化作用經由紅色素及叙 “、、巴素而變成黑色之黑色素之過程乃係黑色素之產生過程。因此，抑制反應之第一階段之酪胺酸酶之作用在抑制黑色素產生上極為重要。防止該黑色素之產生及沈澱之藥劑，即美研發極受期待，至目前為止，已有很多藥劑被開發問市。該藥劑中，有鞣花酸（參考專利文獻丨）、抗壞金酸、氫醌、麴酸、胎盤萃取物及熊果苷等。另外，植物萃取成分也有火棘（Pyracantha fortuneana)(參考專利文獻2)之萃取物、杏仁或模壚之萃取物（參考專利文獻3)、檜木成茉莉等（參考專利文獻4) ’或紅蔥（Eleutherine plicata) (參考專利文獻5)等之報告。 316704D01 3 201242607 專利文獻1 專利文獻2 專利文獻3 專利文獻4 專利文獻5 特開昭64-79103號公報特開2001-139482號公報特開平8-119848號公報特開平11-60467號公報特開平9-25214號公報【發明内容】發明所欲解決之課題然而，以往之黑色素生產抑制劑，就安定性、副作用、功效等而言’難令人滿意，且就供應穩定性或服藥順從性之觀點而言，也難令人滿意之問題。因此’本發明之目的在提供來源於自然，對於人體之安全性高，且供應穩定性無問題而服藥順從性也能令人充分滿意之美白劑。解決課題之手段本發明研究者為解決上述問題經銳意研究之結果，從特定植物最好利用特定溶劑而得之萃取物，發現具有強力之赂胺酸酶活性抑制作用或黑色素合成抑制作用，做為美白用組成物甚為有用。換言之，本發明研究者特別以乙醇等低級醇類之水溶液從櫟木類（oak類；又稱橡木類）等殼斗科櫟屬植物萃取而得之萃取物，可提供美白用組成物，經再三檢討結果完成了本發明。換言之，本發明係關於： (U —種美白劑，含有殼斗科櫟屬植物之溶劑萃取物》 (2)如（1)項之美白劑，其中萃取物係萃取液、萃取液之濃縮物或萃取液之乾燥物。 316704D01 4 201242607 ⑶如(1)項或⑵馆櫟木類。）項之美白劑，其中殼斗科櫟屬植物係 (4)如（！）項至屬植物係呈榷木'類）項中任一項之美白劑，其中殼斗科櫟蘭地酒熟成用、、^^木材所構成之木片、或者威士忌酒或白 ⑸如(C形態者。低級醇類之水溶液（4)項中任一項之美白劑，其中溶劑係含 (6)如（5)項之 ⑺如(6)項-劑，其中低級醇類係乙醇。 1〇〇體積％者。之美白劑’其中溶劑之乙醇滚度係10至物而得者。）項或（7)項之美白劑’其中溶劑係蒸顧含乙醇將二)人^!至（8)項之美白劑’其中溶劑萃取物係藉由 ^ 醇物所得者在橡木财與橡木桶材接觸而得 (1(〇如（9)項之美白劑’其中接觸期間在半年以上。並乂項之美白劑’係威士忌酒、白蘭地酒、或者其浪縮物或乾燥物中之任一種。 (12) 如⑴項至⑴）項巾任_項之美自劑，係属飲食品、香粧品或醫藥品。 (13) 如（12)項之美白劑，係屬外用香粧品或外用醫品。 (14) 如（12)項之美白劑’係屬飲食品、口腔用香极或口服醫藥品。 316704D01 5 201242607 (15) —種飲食品用、香粧品用或醫藥品用之添加劑或調配劑，其特徵為：含有殼斗科櫟屬植物之溶劑萃取物。 (16) —種黑色素產生抑制劑，其特徵為：含有殼斗科櫟屬植物之溶劑萃取物。 (Π)—種殼斗科櫟屬植物之溶劑萃取物之用途，係用於製造美白劑。發明之功效依據本發明之殼斗科櫟屬植物之溶劑萃取物，其美白作用強而安全性高，因此，該溶劑萃取物或含有該溶劑萃取物之組成物可用於製造美白劑（例如具有美白作用之飲食。σ、香粧品或醫藥品等，或飲食用、香粧品用或醫藥品用之添加劑等）。再者，殼斗科櫟屬植物或其溶劑萃取物可做為具有美白作用之飲食品、香粧品或醫藥品之製造原料。【實施方式】實施本發明之最佳形態本發明詳細說明如下：本發明乃關於含有殼斗科櫟屬植物之溶劑萃取物之美白劑。本發明所使用殼斗科（Fagaceae)櫟屬植物（Quercus sp.)之例’可列舉如抱（Quercus serrata Thunb.)、水櫟 (Quercus grosseserrata Blurae, Quercus crispula Blume, Quercus mongolica Fisch. var. grosseserrata(Blume) Rehd. et Wils.)、櫟（Quercus acutissima Carruth.)、雄櫟（Quercus variabilis Blume)、槲（Quercus dentata 316704D01 6 201242607201242607 VI. Description of the Invention: [Technical Field to Which the Invention Is Ascribed] The present invention relates to a whitening agent. More specifically, the whitening of the solvent extract of the genus Fagaceae is a whitening syrup or medicinal product. Double, [Prior Art] Age spots of freckles, freckles and pigmentation on the skin after sun exposure are prone to occur, increase or disappear, and are annoying. The black and middle age of the egg colored for the skin is produced by the melanin produced in the melanocyte of the epidermis; the melanin produced by the melanocyte is diffused to the adjacent cells by the melamine. . The biochemical reaction in the black cell is pushed up as follows, and the tyrosine acid which requires an amino acid is acted upon by tyrosine kinase to become an enzyme or a non-enzymatic oxidation via red pigment and The process of becoming a black melanin is the process of melanin production. Therefore, the action of the first stage of inhibition of tyrosinase is extremely important in inhibiting the production of melanin. The agent that prevents the production and precipitation of melanin, namely US R&D is highly anticipated, and so far, many pharmaceuticals have been developed. This product contains ellagic acid (refer to the patent literature), ascorbic acid, hydroquinone, citric acid, placenta extract and bear. In addition, the plant extracting component is also an extract of Pyracantha fortuneana (refer to Patent Document 2), an extract of almond or mold (refer to Patent Document 3), eucalyptus jasmine, etc. (refer to Patent Document 4). ' or Eleutherine plicata (refer to Patent Document 5), etc. Report 316704D01 3 201242607 Patent Document 1 Patent Document 2 Patent Document 3 Patent Document 4 Patent Document 5 Japanese Patent Application Laid-Open No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. The agent is 'unsatisfactory in terms of stability, side effects, efficacy, etc., and is also unsatisfactory in terms of supply stability or medication compliance. Therefore, the object of the present invention is to provide a source. Naturally, a whitening agent that is highly satisfactory for human body safety and has no problem of supply stability and satisfactory compliance with medication. The means for solving the problem of the present invention is the result of intensive research to solve the above problems, from specific plants. It is preferable to use an extract obtained by using a specific solvent, and it has been found to have potent inhibition of the activity of the glucuronidase activity or inhibition of melanin synthesis, and is very useful as a composition for whitening. In other words, the present inventors particularly use a lower alcohol such as ethanol. An aqueous solution of the type extracted from the genus Eucalyptus (oak; also known as oak), which can be used for whitening. The composition has been reviewed by the results of the review. In other words, the present invention relates to: (U - a whitening agent, a solvent extract containing a plant of the genus Fagaceae) (2) a whitening agent as in (1), The extract is an extract, a concentrate of the extract or a dried extract of the extract. 316704D01 4 201242607 (3) such as (1) or (2) a eucalyptus of the museum.) The whitening agent of the genus, which is a genus of the genus ) A whitening agent such as (!) to the genus of the genus Amaranthus, in which the genus Fritillaria is cooked, the wood is made of wood, or whiskey or white (5) Such as (C form. A whitening agent according to any one of the items (4), wherein the solvent contains (6) (5), and (6), wherein the lower alcohol is ethanol. 1% by volume. The whitening agent' wherein the solvent has an ethanol rolling degree of 10%. Or the whitening agent of item (7), wherein the solvent is distilled to contain ethanol, and the whitening agent of the item (8) is obtained by the use of the alcohol in the oak and the oak. The barrel material is contacted (1 (such as the whitening agent of item (9), which is more than half a year during the contact period. And the whitening agent of the item is a whisky, brandy, or its water or dry matter. (12) The beauty agent of (1) to (1)) is a food or beverage, a cosmetic or a pharmaceutical product. (13) The whitening agent as in (12) is a topical cosmetic or external medicine. (14) The whitening agent in item (12) is a food or beverage, oral fragrance or oral pharmaceutical product. 316704D01 5 201242607 (15) An additive for food, beverage, cosmetic or pharmaceutical use or A compounding agent characterized by: a solvent extract containing a plant of the genus Fagaceae. (16) A melanin production inhibitor characterized by a solvent extract containing a plant of the genus Fagaceae (Π)- The use of a solvent extract of the genus Fagaceae to produce a whitening agent. The solvent extract of the genus Fagaceae according to the present invention has strong whitening effect and high safety. Therefore, the solvent extract or the composition containing the solvent extract can be used for the manufacture of a whitening agent (for example, having a whitening effect) Diet, σ, cosmetics or pharmaceuticals, or additives for food, cosmetics, or pharmaceuticals. In addition, the genus Fagaceae or its solvent extract can be used as a food and drink product with whitening effect. BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a whitening agent containing a solvent extract of the genus Fagaceae, which is used in the present invention. Examples of the family Quercus sp. of the Fagaceae can be cited as Quercus serrata Thunb., Quercus grosseserrata Blurae, Quercus crispula Blume, Quercus mongolica Fisch. var. grosseserrata (Blume) Rehd Et Wils.), Quercus acutissima Carruth., Quercus variabilis Blume, Quercus dentata 316704D01 6 201242607

Thunb.)、抱槲（Quercus aliena blume)、姥芽槲（Quercus phillyraeoides A. Gray)、鐵構（Quercus myrsinaefolia Blume, Cyclobalanopsis myrsinaefolia(Blume) Oerst.)、儲（Quercus glauca Thunb., Cyclobalanopsis glauca(Thunb.)0erst.)、衝羽根儲（Quercus paucidentata Franch., Quercus salicina Blume, Cyclobalanopsis paucidentata Kudo et Masam., Quercus sessilifolia Blume, Cyclobalanopsis sessilifolia Blume)、白背櫧（Quercus stenophylla Makino, Quercus salicina Blume, Cyclobalanopsis salicina(Blume) Oerst.)、縞紋儲（Quercus glauca Thunb. var. fasciata Blume)、飛龍儲（Quercus glauca Thunb. var. lacera Matsum.)、血儲（Quercus acuta Thunb., Cyclobalanopsis acuta(Thunb.) Oerst.)、石儲（Quercus gilva Blume, Cyclobalanopsis gilva(Blume)Oerst.)、白櫟（Quercus alba L.)、阿利桑那白櫟（Quercus arizonica)、沼澤白櫟 (Quercus bicolor Wi lid.)、伊大利櫟（Quercus cerris L.)、阿利桑那低櫟（Quercus chrysolepis Liebm.)、黑傑克櫟（Quercus mari landica)、石栗（Quercus cornea Lour.， Lythocarpus cornea(Lour. )Rehd.)、真櫟（Quercus gambelii Nutt.)、葉櫟（Quercus agrifolia Nee)、藍櫟 (Quercus douglasii)、美國黑櫟（Quercus nigra)、棕櫟 (Quercus palmeri)、針櫟（Quercus palustris)、加州低櫟（Quercus dumosa)、愛美麗櫟（Quercus emoryi Torr.) ' 316704D01 7 201242607 聳櫟（Quercus engelmanni i Greene)、奥勒岡白櫟（Quercus garryana Dougl)、加州白櫟（Quercus lobata Nee)、黑櫟 (Quercus velutina)、加州黑櫟（Quercus kelloggii)、大果櫟（Quercus macrocarpa)、波葉櫟（Quercus undulata Torr.) ' 軟木櫟（Quercus lucombeana Sweet, Quercus suber L.)、聖櫟（Quercus ilex L.)、琉球白背櫟（Quercus miyagii Koidz., Cyclobalanopsis raiyagii(Koidz.)Kudo et Masamune)、小櫟（Quercus pungens)、蒙古抱（Quercus mongolicaFisch. var· mongolica)、栗櫟（Quercus prinus L·)、英國櫟（Quercus robur L.)、西班牙櫟（Quercus falcata)、北方血櫟（Quercus rubra)、維吉尼雅櫟 (Quercus virginiana)、内陸櫟（Quercus wislizeni)、星狀櫟（Quercus stellata)、高山櫟（Quercus semicarpif0lia Sm )、無柄櫟（Quercus 咐咖 (Mattuschka)Lieblein)等。自古做為威士忌酒或白蘭地酒等之製造、貯藏用酒桶之原料之多數植物皆屬於該屬種類。特別是被稱為櫟木類（oak類）之植物種類為較佳。本發明中所指櫟木類乃係殼斗科櫟屬植物中，威士忌酒或白蘭地酒等之製造、貯藏用酒桶之原料所使用之植物群。本發明中可善加利用該櫟木類。其中以白櫟、英國櫟、無柄櫟、西班牙櫟、大果櫟或水櫟等為最佳。就上述植物而言，做為原料而使用之部位並無特別限 :，樹幹、葉、枝、樹皮、花、果實等皆可利用，但以從于幹及主枝除去樹皮之心材中萃取為宜。又，萃取可在採 316704D01 8 201242607 取後立即進行，或於乾燥後進行。必要時可經粉碎、裁斷、切細成形等加工後再使用。由上述植物之木材製得之切片、木粉、木桶等屬於上述加工品範園。木桶在溶劑萃取前，以將内壁用火加熱處理為較宜。本發明中所使用之萃取溶劑，以低級醇類之水溶液為較佳。上述低級醇類指碳數丨至4之醇類（例如T醇、乙醇、丙醇、丁料）。切液巾之低級醇類濃度以能萃取得美白作用強之萃取物為要，具體言之，低級醇類水溶液中之低級醇類濃度，通常在約10至1〇〇體積％範圍，其中以約3〇至99體積％為較佳。倘若考慮最終調配在飲食品等中，萃取/合劑就文全性觀點而言，以使用乙醇水溶液為較佳。又，所述萃取溶劑’除低級醇類和水之外’在不會大幅度損及萃取效率範圍下，尚可含有其他成分。例如必要時可含有糠類、鹽類或胺基酸等水溶性成分或各種其他溶劑（例如乙酸乙酯、丙酮等）。 ϋ〜叫門如乙醇為低級醇類時，乙醇水溶液可用業用級和水〈處合物，或各種酒精製品或其半成品例如白蘭地酒、咸士忌酒、白酒、日本清酒、啤酒、發〜二，㉟Α特加酒或其半製品等。其製造方法可按仃使用植物原料製成木桶，注人溶劑於其中進「^ 使用额乙醇含有物所得者為較佳。上二芽乃;蒸觸含乙醇之溶液所得八士將麥芽、米、葡萄等作為原料之一 77 化發酵所得之乙醇含有物，經單式蒸顧或複 316704D01 9 201242607 蒸=而製成者。例如以使用燒酒、伏特加酒、威士忌酒貯藏刖原/酉（例如麥芽威士忌原酒之新壺（咖⑽）、榖物威士忌原酒之新酒（new make))、白蘭地酒貯藏前原酒（即 ° μ ^地时贿㈣、白蘭地原酒為更佳。其製造方法可按照t法實施。該時，其卒取條件以室溫下進行約半年至別年左右為較佳。制巾做為原料植物之溶料取方法並無特別限料形成桶等容器，其二然後’靜置神，或加熱迴μ浸依照周知方法視期望之性質㈣—。^取方法係或加溫下進行。萃取溫度_ 7 w卒取可在常溫溶劑之沸點以下之溫度為制，但在操作上，以在萃取方法而異，通常在約3卜=所需時間隨溫度條件或卯分鐘以上。對於萃取時問夕μ :無特殊限制’大多數情泥約3。年本發明亦包括30年以上。 ^虽然’ 依據本發明，於上述萃取後藉由 ί斗科櫟屬植物，其處理物或其加卫品與含^白成分^ 卒取液加以分離。齡離方法可依關知方法，例，過據等而實施。本發明可以將萃取液提供美白劑使用，也可將萃取液之=物或乾燥物（濃縮乾涸物）做為美用。該濃縮:：厂堅或減壓下進行。：積減少成約5至7〇細，其中以減少成約10至50體積/ 為較佳。㈣物可由含有美體積發。 316704D01 201242607 溶劑而製得。再者，本發明之溶劑萃取物也包括萃取所得萃取物再經例如I柱層析法等分離精製而成者。如此所得之溶劑萃取物可以完成萃取操作所得之萃取液，部分去除萃取液之浴劑而成之濃縮物，或完全去除溶劑之乾固物之狀態使用。就保存安定性或容易搬運之觀點而言，以使用乾燥物為較佳。本發明所謂溶劑萃取物乃指上述萃取液、濃縮物或乾燥物。又，製成含有本發明之溶劑萃取物之美白用組成物，該含有具備美白作用之上述萃取物之組成物可直接做為美白劑使用’，另外，亦可例如添加氧化鈦、碳酸鈣、蒸餾水、乳糖、殿粉或下列實施例所記載之具體例等適當液態或固態之賦形劑或增量劑後而做為美白劑使用。美白劑中之溶劑萃取物之混合比例別無限制，依據萃取物之性狀（例如萃取液、濃縮物或乾燥物），例如可適當地設定在約〇. 01至100重量％範圍。又，依據本發明可調製成含有殼斗科櫟屬植物之溶劑萃取物之飲食品、香粧品及醫藥品等。溶劑萃取物之調配比例別無限制’視萃取物之性狀（例如萃取液、濃縮或乾燥物），例如可調配在約〇♦01至1〇〇重量％範圍’其中以適度設定在約0. 1至80重量％範圍為較佳。上述飲食品，例如在水飴、含錠、口香糖、養樂多、冰溪淋、布丁、果凍、水羊羹、酒精飲料、咖啡飲料、純果汁、果汁飲料、碳酸飲料、清涼飲料、牛奶、乳液飲料、乳酸菌飲料等中含有適量之溶劑萃取物而提供為飲食品。 316704D01 11 201242607 該飲食品在必要時依照常法調配各種添加劑而製造之。調製該飲食品時，例如可將—般做為食品㈣使用之下列添加劑’例如葡萄糖、果糖、餘、麥芽糖、山梨醇、甜菊精（stevioside)、甜茶素（rub咖⑽）、玉米糖聚、乳糖、枸櫞酸、酒石酸、縣酸、號_、乳酸、卜抗壞血酸、cH-α-生育酴、異抗壞血酸納（s〇d邮以如）、甘油丙一醇甘/由脂肪酸酿、聚甘油脂肪酸醋、脂肪酸蔬糖醋、山梨騎脂肪酸g|、脂肪酸丙二醇酯、阿㈣膠、角叉菜膠、㈣白、明膠、果膠、石花菜（瓊脂）、維生素 B類、於親胺、泛_、胺基酸類、触類、色素、香料、保存财依照常法適量調配而製造之。本發明巾所謂㈣品乃包括被稱為化粧品或香料製品 ^〇〇 &供本發明之溶劑萃取物時，可在化粧水、化粧乳霜、乳液、粉底、口紅、整髮料、生髮水、生髮劑、洗 =、’閏濕精、沐浴劑等非π腔用之香粧品、或牙膏、漱口劑、洗口液、σ腔香料#σ腔狀香粧品中含有適量之 _萃㈣而製成香輕品。 5香粧。σ可適度配入一般作為香粧品原料使用之下列劑’例如植物油等油脂類、羊毛脂或蜜躐等躐類、碳素風類1旨肪酸、高級醇類、_、㈣界面活性劑、色 =+香料維生素類、植物、動物性萃取成分、紫外線吸收^劑、尸备儿暫λ 劑、防腐•殺菌劑、保濕劑（例如尿素、透明筲酸）等，並按照常法而製造之。並含仏為邊藥品使用時，必要時可配入各種添加劑 316704D01 12 201242607 #適量之溶劑萃取物而製成各種劑型之醫藥品。例如疑劑、膠囊劑、顆粒劑、散劑、糖聚劑、：醫藥品，或軟膏、眼用軟膏、洗潔劑、乳霜、貼劑、點眼劑、注射劑等非經口醫藥品而提供。該醫藥品可使用各種添加劑依照常法而製造。所使用添加添加劑無特殊限制’可採用-般使用者，例如澱粉、乳糖、白糖、甘路醇、羧甲基纖維素、玉米澱粉、無機鹽等固形載劑、蒸餾水、生理食鹽水、葡萄糖水溶液、乙醇等醇類、或丙二醇、聚乙二醇等液體載劑、各種動植物性油、白色凡士林、石蠟、蠟等油性載劑等。使用乙醇水丨谷液作為溶劑時，或使用飲食經驗豐富之櫟木類之萃取液作為原料植物時，由於經口服用時之安全性甚優’所以適合作為飲食品、經口醫藥品、口腔用香粧品等。因此’可使用威士忌酒或白蘭地酒，或其濃縮物以及乾燥物作為溶劑萃取物，調製成適當之飲食品、經口醫藥品、口腔用之香粧品。又，使用本發明之溶劑萃取物調製飲食品、香粧品或醫藥品時，也可併用其他美白劑’或黑色素生產抑制劑，例如辅花酸、抗壞血酸、氫酿、麴酸、胎盤萃取物、熊果苷、或火棘、杏仁、木瓜、扁柏、茉莉、紅蔥等植物之萃取成分等。該植物萃取成分和本發明之溶劑萃取物之調配比例雖不能一概而論，通常以重量比率計約在i: 9至9: 1範圍。本發明中所谓飲食品用、香粧品用或醫藥品用之添加 316704D01 13 201242607 劑或調配劑乃指香料、色素、抗氧化劑等飲食品、香粧品或醫藥品上通常使用之添加劑或調配劑中混合以溶劑萃取物者。其混合比率可適加設定又疋之。一般，其混合比率在例如約0.01至100重量％範圍，1中甲以〇. 1至8〇重量％為敕佳。此處所使用飲食品、香粧口七^ 里篁祕劑如同上述各種添加劑。以樂品祕加劑或調配實施例在其2明據實施例更詳細說明如下。但是本發明不紐 (試驗方法）酪胺酸酶抑制活性之坪估方法 ^實施射，評⑽__卩制活性㈣為美白作用之指標。試驗方法如下。 ^鼠黑色素瘤細胞在5%二氧化碳、咖之條件下， Γ胎兒血清之咖培養基培養之。被檢驗物質私傲& 4田地'合解;東結乾燥品而提供於試驗。將被檢驗、由B16黑色素瘤細胞調製成之赂胺酸酶粗酵素液混。。添加作為基質之[_多巴並使其最終濃度為。.娜。在下反應2〇分鐘，測定492nm之吸光度^吸光度a和夕巴色素量成比例。關於對照組，將上述反應系中未添加被檢驗試料者進行同樣操作而測定其492nm之吸光度b，並按照下式計算酪胺酸活性抑制率。抑制率（％) = (l-A/B)xl〇〇以梯度方式改變被檢驗試料濃度（eg/反應溶液ml)並測定上述抑制率，由内插法求得抑制率為50%時之試料濃 316704D01 14 .201242607 ，度，以該濃度做為ic5〇。實施例1 採討白櫟萃取物之有無對於美白作用之影響。 (發明製品1): 將工業用乙醇與水混合，成為60體積％之乙醇水溶液。在該乙醇水溶液（2. 4L)中添加白櫟木片（lxlx2cm) (240g)，在85°C下加熱5分鐘後，室溫下放置24小時，再於85°C下加熱5分鐘。所得萃取液經減壓乾燥而得乾燥製品（7. 2g)。 (發明製品2至5): 調製威士忌酒貯藏前原酒使用之新壺（new pot)。即，粉碎發芽之大麥（麥芽），混合溫水而行糖化，加入酵母於過濾之糖液使之發酵，而得酒精度數為7.0至7. 5體積％之醪。放入該醪於銅質單式蒸餾器中，蒸餾二次，而得酒精濃度為60體積％之含酒精組成物（即新壺）。其次，使用白櫟製造威士忌酒製造用之酒桶（内容量為 230L)。酒桶内壁用直火加熱處理之。該酒桶中放入210L之上述酒精溶劑（即新壺），加栓塞後，室溫下保存於貯藏庫中。經時採取萃取液，於3年（發明製品2)，5年（發明製品3)，12年（發明製品4)，18年（發明製品5)之時點採取之。將所得萃取液減壓乾燥，做為被檢驗物質。 (發明製品6): 將按照相同方法製造且保存期間12年以上之萃取物 316704D01 15 201242607 數種換合所得之山多利威士忌山崎（註冊商襟名）12 減壓乾燥，得到被檢驗物質（發明製品6)。予以依照上述方法測定該發明製品之酪胺醆酶抑制舌座關於對照品，使用新壺經減壓乾燥者（對 ' 。結果示於表b 1)。其較之對照品，本發明製品皆確認有強力活性。特別是使用新壺做為溶劑時，保存期抑制愈強。 t瑚間愈長其作用與多種化粧品或外用醫藥品中使用做為同試驗系評估之結果(-I 乃表00顯示具有與鞣花酸同等以上之強力效果。 =上述可知本發明製品具備強力美白作用，特別是保 =精長其美白作用愈強。這些製品由於以乙醇水溶液作為溶劑，讀照飲食經驗豐富之威士忌酒之製造方法製成’因此可提供具奴可供σ服之高安全性之美白劑。 316704D01 16 201242607 .表1 被檢驗試料酪胺酸酶抑制活性 JCs〇(jiS^2_____ 發明製品1 白櫟木片萃取物 99 ______ ______----- 發明製品2 室溫保存3年 _____ 發明製品3 室溫保存5年 ___- 發明製品4 室溫保存12年 52_____ 發明製品5 室溫保存18年發明製品6 山多利威士忌山崎 (註冊商標）12年 50 _一一----- 對照品1 新壺之乾燥品實施例2 探討英國櫟萃取物有無對於美白作用之影響。 (發明製品7): 將工業用乙醇與水混合成為7Q體積％之乙醇水溶液。在該乙醇水溶液（10L)中，添加為英國櫟之一種之利姆山櫟 lkg經細切者，在85t：下加熱5分鐘後，放置室温下24小夺再於85C下加熱5分鐘。所得萃取液經減壓乾燥而付 148g之乾燥品。 (發明製品8至11): 衣做為白蘭地酒貯藏前原磨碎白葡萄，取果汁母使崎。即， 8至10體m之葡萄發酵液。在而得酒精濃度、餾器十蒸餾而得含有酒 316704D01 201242607 精濃度70體積％之含酒精組成物（n〇uvelle)。接下來’使用英國櫟製造白蘭地製造用桶（内容量： 370L)。酒桶内壁用直火加熱處理之。其次’將上述乙醇溶劑（即n〇uvelle)350L裝入該白蘭地酒製造用桶中加以栓塞，在貯藏庫中於室溫下保存之。經時採取，於7年（發明製品8)，1〇年（發明製品9)，15 年（發明製品1〇) ’ 20年（發明製品u)之時點採取，將所得萃取液減壓乾燥，作為被檢驗物質。 (發明製品12): 將按照相同方法長期貯藏所得之萃取物數種混合而得之「山多利白蘭地最優」（註冊商標）減壓乾燥，得到被檢驗物質（發明製品12)。按照上述方法測定各發明製品之酪胺酸酶抑制活性。關於對照品，使用nouvelle經減壓乾燥者（對照品 2)。其結果示於表2。較之對照品，本發明製品皆確認具有強力酪胺酸酶抑制活性。特別是使用nouveiie作為溶劑時，保存期間愈長 316704D01 201242607 表2 被檢驗試料厂酷胺酸酶抑制活性 IC5〇( // g/ml) 發明製品7 英國櫟萃取物 411 發明製品8 室溫保存7年 482 發明製品9 室溫保存1 〇年 413 發明製品10 室溫保存15年 228 ' 發明製品11 室溫保存20年 97 發明製品12 山多利白蘭地最優 (註冊商榡） 109 對照品2 nouvelle 之敖、鹿 -----乙你口口 10000以上較之對照品，本發明製品皆確認具有強力之酪胺酸酶抑制活性。特別是使用n〇uvelle為溶劑時，保存期間愈長其作用愈強。由上述顯示本發明製品之美白作用強，特別是保存期間愈長其美白作用愈強。這些製品由於使用乙醇水溶液做為溶劑，且按照飲食經驗豐富之白籣地酒之製造方法而製成，所以可提供具有足可供口服之高安全性之美白劑。實施例3 使用發明製品6評估其細胞内黑色素生產抑制作用。被檢驗物質使用上述發明製品6(即山多利威士忌山崎 (註冊商標）12年）。即’將山多利威士忌山崎（註冊商標）12 年加以減壓乾燥，以最終濃度為1〇〇//g/ml而使用。 316704D01 201242607 細胞内黑色素量按照下述方法測定之，將4x1 G4個B16 黑色素瘤細胞放置在6Qmm之塑膠f培養凰中進行預培養。經24小時之預培養後添加被檢驗物質。於被檢驗物質存在下，再培養細胞3日之後，以PBS洗淨，加入1N之氫氧化納並加熱溶解。測定培養液之4?()nm處之吸光度c。吸光度C和黑色素量成比例。關於對照品，將上述反應系中未添加被檢輯料者輯同獅作後，敎其47〇nm處之吸光度D，再藉由下式計算細_黑色素生產抑制率。抑制率（％) = (1~C/D)xl00 又’同時計測細胞數目，探討試料對於細胞響。其結果示於表3。〜表3Thunb.), Quercus aliena blume, Quercus phillyraeoides A. Gray, Quercus myrsinaefolia Blume (Cyclobalanopsis myrsinaefolia (Blume) Oerst.), Quercus glauca Thunb., Cyclobalanopsis glauca (Thunb .)0erst.), Quercus paucidentata Franch., Quercus salicina Blume, Cyclobalanopsis paucidentata Kudo et Masam., Quercus sessilifolia Blume, Cyclobalanopsis sessilifolia Blume, Quercus stenophylla Makino, Quercus salicina Blume, Cyclobalanopsis salicina Blume) Oerst.), Quercus glauca Thunb. var. fasciata Blume, Quercus glauca Thunb. var. lacera Matsum., Quercus acuta Thunb., Cyclobalanopsis acuta (Thunb.) Oerst. ), Quercus gilva Blume, Cyclobalanopsis gilva (Blume) Oerst., Quercus alba L., Quercus arizonica, Quercus bicolor Wi lid., Italy Quercus cerris L., Quercus chrysolepis Liebm., Black Jack (Quer) Cus mari landica), Quercus cornea Lour., Lythocarpus cornea (Lour.) Rehd., Quercus gambelii Nutt., Quercus agrifolia Nee, Quercus douglasii, American black pheasant Quercus nigra), Quercus palmeri, Quercus palustris, Quercus dumosa, Quercus emoryi Torr. '316704D01 7 201242607 Qu (Quercus engelmanni i Greene), Åre Quercus garryana Dougl, Quercus lobata Nee, Quercus velutina, Quercus kelloggii, Quercus macrocarpa, Quercus undulata Torr. 'Quercus lucombeana Sweet, Quercus suber L., Quercus ilex L., Quercus miyagii Koidz., Cyclobalanopsis raiyagii (Koidz.) Kudo et Masamune), Quercus pungens , Mongolian hug (Quercus mongolicaFisch. var. mongolica), chestnut (Quercus prinus L.), British cockroach (Quercus robur L.), Spanish cockroach (Quercus falcata), northern blood cockroach (Quercus rubra), Quercus virginiana, Quercus wislizeni, Quercus stellata, Quercus semicarpif0lia Sm, and stalkless Quercus (Mattuschka Lieblein) Wait. Most of the plants that have been used as raw materials for the manufacture and storage of whiskeys such as whiskey or brandy belong to this genus. In particular, plant species known as oysters (oaks) are preferred. In the present invention, the eucalyptus is a plant group used in the manufacture and storage of casks of whiskey or brandy in the genus Fagaceae. The eucalyptus can be utilized in the present invention. Among them, white carp, English scorpion, sessile scorpion, Spanish scorpion, big fruit scorpion or leeches are the best. In the case of the above-mentioned plants, the parts to be used as raw materials are not particularly limited: trunks, leaves, branches, bark, flowers, fruits, and the like are available, but are extracted from the heartwood from which the bark is removed from the stem and the main branches. should. Further, the extraction can be carried out immediately after taking 316704D01 8 201242607 or after drying. If necessary, it can be processed by crushing, cutting, and cutting. Slices, wood flour, wooden barrels, etc. made from the wood of the above plants belong to the above-mentioned processed products. It is preferred to heat the inner wall with fire before the solvent extraction. The extraction solvent used in the present invention is preferably an aqueous solution of a lower alcohol. The above lower alcohols are alcohols having a carbon number of 丨 to 4 (for example, T alcohol, ethanol, propanol, butylene). The lower alcohol concentration of the liquid wiper is preferably an extract capable of extracting a whitening effect, in particular, the lower alcohol concentration in the aqueous solution of the lower alcohol is usually in the range of about 10 to 1% by volume, wherein Approximately 3 to 99% by volume is preferred. In view of the fact that the final blending is in foods and drinks, etc., it is preferred to use an aqueous ethanol solution from the viewpoint of the completeness of the extraction/mixture. Further, the extraction solvent 'except for the lower alcohol and water' may contain other components without significantly impairing the extraction efficiency range. For example, a water-soluble component such as an anthracene, a salt or an amino acid or various other solvents (e.g., ethyl acetate, acetone, etc.) may be contained as necessary. ϋ 叫叫叫乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇乙醇Second, 35 Α special wine or its semi-products. The manufacturing method can be made into a wooden barrel according to the use of plant materials, and the solvent is preferably used in the "^ using the amount of ethanol contained in the product. The upper two buds; the steamed contact with the ethanol-containing solution to obtain the malt. The ethanol-containing material obtained by the fermentation of rice, grapes, etc., as a raw material, is produced by a single steaming or steaming of 316704D01 9 201242607. For example, using shochu, vodka, whiskey to store 刖酉 / 酉(For example, the new pot of malt whisky original wine (caffe (10)), the new make of the whiskey original wine (new make), the brandy of the brandy before the storage of the brandy (ie, the bribe (4), the brandy of the brandy is better. It can be carried out according to the method of t. At this time, the stroke condition is preferably carried out at room temperature for about half a year to about another year. The method for preparing the solvent as a raw material plant is not particularly limited to form a container such as a barrel. Secondly, 'remaining the god, or heating back to the μ immersion according to the well-known method according to the desired properties (4) - ^ method is taken or heated. Extraction temperature _ 7 w stroke can be at the temperature below the boiling point of the solvent at room temperature But in operation , depending on the extraction method, usually at about 3 times = the required time with temperature conditions or more than 卯 minutes. For the extraction time μ μ : no special restrictions 'most of the mud about 3. The year of the invention also includes 30 years Above. ^Although, according to the present invention, after the above extraction, the treatment substance or its edgy is separated from the white matter containing the stroke liquid by the genus Physalis, and the age separation method can be determined according to the method. The invention can be used as a whitening agent, and the extract or the dried product (concentrated dry matter) can be used as a beauty. The concentration:: firm or decompression The following is carried out: The product is reduced to about 5 to 7 inches, wherein it is preferably reduced to about 10 to 50 volumes/(4). The material can be obtained by containing a solvent of 316704D01 201242607. Further, the solvent extract of the present invention The extract obtained by the extraction is further separated and purified by, for example, I column chromatography, etc. The solvent extract thus obtained can complete the extract obtained by the extraction operation, partially remove the concentrate of the extract, or Complete removal of solvent It is preferable to use a dry matter from the viewpoint of preserving stability or being easy to handle. The so-called solvent extract in the present invention means the above-mentioned extract, concentrate or dried product. In the whitening composition of the solvent extract of the invention, the composition containing the above-mentioned extract having a whitening effect can be directly used as a whitening agent, and, for example, titanium oxide, calcium carbonate, distilled water, lactose, and temple powder can be added. Or a suitable liquid or solid excipient or extender as the whitening agent in the specific examples described in the following examples. The mixing ratio of the solvent extract in the whitening agent is not limited, depending on the properties of the extract ( For example, the extract, the concentrate or the dried product may be suitably set, for example, in the range of about 0.1 to 100% by weight. Further, according to the present invention, foods and drinks, cosmetics, and pharmaceuticals containing a solvent extract of the genus Fagaceae can be adjusted. The proportion of the solvent extract is not limited to 'the characteristics of the extract (such as extract, concentrated or dried), for example, can be adjusted in the range of about 〇 ♦ 01 to 1 〇〇 wt% 'where the moderate setting is about 0. A range of from 1 to 80% by weight is preferred. The above foods and drinks, for example, in leeches, ingots, chewing gum, Yakult, ice squirt, pudding, jelly, water alpaca, alcoholic beverages, coffee drinks, pure juices, juice drinks, carbonated drinks, refreshing drinks, milk, lotion drinks, lactic acid bacteria A beverage or the like contains an appropriate amount of a solvent extract and is provided as a food or drink. 316704D01 11 201242607 This food and drink is manufactured by mixing various additives according to the usual method when necessary. When preparing the food or drink, for example, the following additives such as glucose, fructose, residual, maltose, sorbitol, stevioside, stevia (rub coffee (10)), corn candy, can be used as food (4). Lactose, citric acid, tartaric acid, acid, _, lactic acid, ascorbic acid, cH-α-tocopherol, sodium erythorbic acid (s〇d), glycerol, glycerol, fatty acid, polyglycerol Fatty acid vinegar, fatty acid vegetable sweet and sour vinegar, Yamanashi riding fatty acid g|, fatty acid propylene glycol ester, A (tetra) gum, carrageenan, (four) white, gelatin, pectin, stone cauliflower (agar), vitamin B, in nucleophilic, pan _, amino acids, touches, pigments, spices, and preserved money are manufactured according to the appropriate amount of conventional methods. The so-called (four) product of the present invention includes a so-called cosmetic or perfume product, when used in the solvent extract of the present invention, in a lotion, a cosmetic cream, an emulsion, a foundation, a lipstick, a hair styling, a hair styling water. , hair restorer, wash =, '闰湿精, bathing agent and other non-π cavity cosmetics, or toothpaste, mouthwash, mouthwash, σ cavity spice #σ cavity-like cosmetics contain the right amount of _ extract (four) It is made into a fragrant light product. 5 fragrance makeup. σ can be appropriately blended into the following agents generally used as raw materials for cosmetic products, such as oils such as vegetable oils, lanolins such as lanolin or candied fruit, carbonic acids, fatty acids, higher alcohols, _, (iv) surfactants, Color = + spice vitamins, plant, animal extracts, UV absorbers, corpse preparations, antiseptics, fungicides, moisturizers (such as urea, transparent tannic acid), etc., and manufactured according to common law . When it is used as a side-effect medicine, it can be formulated with various additives if necessary. 316704D01 12 201242607 #Appropriate amount of solvent extract to prepare various dosage forms of medicines. For example, suspects, capsules, granules, powders, sugar-polymerizing agents, pharmaceuticals, or ointments, ophthalmic ointments, detergents, creams, patches, eye drops, injections, etc. . The pharmaceutical product can be produced according to a conventional method using various additives. The additive to be added is not particularly limited. It can be used by general users, such as starch, lactose, white sugar, glycol alcohol, carboxymethyl cellulose, corn starch, inorganic salt and other solid carriers, distilled water, physiological saline, and aqueous dextrose solution. Alcohols such as ethanol, liquid carriers such as propylene glycol and polyethylene glycol, various animal and vegetable oils, oily carriers such as white petrolatum, paraffin wax, and wax. When using ethanol water glutinous rice liquid as a solvent, or when using an extract of eucalyptus, which is rich in dietary experience, as a raw material plant, it is excellent in safety when it is used orally, so it is suitable as a food, drink, oral medicine, oral cavity. Cosmetics and so on. Therefore, whiskey or brandy, or a concentrate thereof, and a dried product can be used as a solvent extract to prepare a suitable food or drink, oral medicine, or oral cosmetic. Further, when the food or beverage, the cosmetic or the pharmaceutical product is prepared by using the solvent extract of the present invention, other whitening agents or melanin production inhibitors such as acaciaric acid, ascorbic acid, hydrogen brewing, citric acid, placental extract, and the like may be used in combination. Arbutin, or extracts of plants such as Pyracantha, almond, papaya, cypress, jasmine, and red onion. The blending ratio of the plant extract component and the solvent extract of the present invention cannot be generalized, and is usually in the range of i: 9 to 9: 1 by weight. In the present invention, the use of 316704D01 13 201242607 or a formulation for the use of foods, cosmetics, cosmetics, or pharmaceuticals refers to additives or formulas commonly used in foods, cosmetics, cosmetics, and the like, such as perfumes, colors, and antioxidants. Mix with solvent extract. The mixing ratio can be adjusted and set. In general, the mixing ratio thereof is, for example, in the range of about 0.01 to 100% by weight, and in the case of 1 to 8% by weight. The foods and beverages and the fragrant makeup products used here are like the above various additives. The following is a more detailed description of the embodiment of the present invention. However, the present invention is not a new method (test method) tyrosinase inhibitory activity ping method ^Impression, evaluation (10) __ 卩 activity (4) is an indicator of whitening effect. The test method is as follows. Mouse murine melanoma cells were cultured in 5% fetal carbon dioxide, coffee conditions, and fetal serum. The substance to be tested is arbitrarily & 4 field 'reconciliation; East knot dry product is provided for testing. It will be tested and mixed with B1 melanoma cells to form a glutamate enzyme. . Add [_dopa as a substrate and make it the final concentration. Na. After the next reaction for 2 minutes, the absorbance at 492 nm, the absorbance a, and the amount of the pigment were measured. In the control group, the absorbance b at 492 nm was measured in the same manner as in the above reaction system without adding the test sample, and the inhibition ratio of tyrosine activity was calculated according to the following formula. Inhibition rate (%) = (lA/B)xl〇〇 The concentration of the test sample (eg/reaction solution ml) was changed in a gradient manner and the above inhibition rate was measured, and the sample concentration at 50% inhibition rate was determined by interpolation. 316704D01 14 .201242607 , degrees, at this concentration as ic5 〇. Example 1 The presence or absence of extract of the white peony was investigated for the effect of whitening action. (Invention product 1): Industrial ethanol was mixed with water to obtain a 60% by volume aqueous ethanol solution. White eucalyptus tablets (lxlx2 cm) (240 g) were added to the aqueous ethanol solution (2.4 L), and the mixture was heated at 85 ° C for 5 minutes, left at room temperature for 24 hours, and further heated at 85 ° C for 5 minutes. The obtained extract was dried under reduced pressure to give a dried product (7.2 g). (Inventive Products 2 to 5): A new pot used for the original sake of the whisky before storage. 5% 醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪醪. The crucible was placed in a copper single distiller and distilled twice to obtain an alcohol-containing composition (i.e., a new jug) having an alcohol concentration of 60% by volume. Secondly, the use of white oysters to make whiskeys for the manufacture of whisky (content is 230L). The inner wall of the barrel is heated by direct fire. 210L of the above alcohol solvent (ie, new pot) was placed in the wine barrel, and after embolization, it was stored in a storage room at room temperature. The extract was taken over time to take it at 3 years (Innovative Product 2), 5 years (Inventive Product 3), 12 Years (Inventive Product 4), and 18 Years (Inventive Product 5). The resulting extract was dried under reduced pressure to be a substance to be tested. (Invention product 6): The Santo Dolly Yamazaki (registrar nickname) 12, which was produced by the same method and stored for more than 12 years in the storage period, was 316704D01 15 201242607, and was dried under reduced pressure to obtain a substance to be inspected (inventive) Article 6). The tyrase chymase inhibiting tongue of the inventive product was measured according to the above method. For the reference substance, the new pot was dried under reduced pressure (for '. The results are shown in Table b 1). Compared with the control, the articles of the present invention were confirmed to have strong activity. In particular, when a new pot is used as a solvent, the shelf life is suppressed more strongly. The longer the interaction between the corals and the various cosmetic or topical pharmaceutical products, the results of the evaluation of the same test system (-I is that Table 00 shows a strong effect equal to or higher than ellagic acid. The whitening effect, especially the protection of the long-term effect of the whitening effect, is stronger. These products are made by using the aqueous solution of ethanol as a solvent and the method of manufacturing the whisky that is experienced in the diet. Therefore, it can provide a high security for slaves. Sexual whitening agent. 316704D01 16 201242607 . Table 1 Tested tyrosinase inhibitory activity JCs〇(jiS^2_____ Invention product 1 White eucalyptus extract 99 ______ ______----- Invention product 2 Storage at room temperature for 3 years _____ Invention product 3 Storage at room temperature for 5 years ___- Invention product 4 Storage at room temperature for 12 years 52_____ Invention product 5 Storage at room temperature for 18 years Invention product 6 Santolee whisky Yamazaki (registered trademark) 12 years 50 _一一--- -- Reference 1 Dry product of the new pot Example 2 To investigate the effect of the British cockroach extract on the whitening effect (Inventive product 7): Mixing industrial ethanol with water to make 7Q vol% ethanol In the aqueous solution of ethanol (10 L), the limings of lyme, which is a kind of British cockroach, are finely cut, heated at 85t: for 5 minutes, then placed at room temperature for 24 ounces and then heated at 85 °C for 5 minutes. The obtained extract was dried under reduced pressure to give 148 g of dried product. (Invention products 8 to 11): The clothes were used as the original ground white grapes before the brandy storage, and the juice mothers were used to make the skin. That is, the grapes of 8 to 10 m The fermentation broth is obtained by distilling the alcohol concentration and the distillation apparatus to obtain an alcoholic composition (n〇uvelle) containing 316704D01 201242607 and a concentration of 70% by volume. Next, 'Using British 栎 to make a barrel for brandy manufacturing (content amount: 370L). The inner wall of the barrel is heat treated by direct fire. Next, '350 ml of the above ethanol solvent (ie n〇uvelle) is placed in the barrel of the brandy for embedding, and stored in the storage at room temperature. It is taken at the time of 7 years (invention product 8), 1 year (invention product 9), 15 years (invention product 1 〇) '20 years (invention product u), and the obtained extract is dried under reduced pressure as The substance to be inspected (invention product 12): will be pressed In the same manner, the extract obtained by long-term storage is mixed and the "Sandoli Brandy Best" (registered trademark) is dried under reduced pressure to obtain a test substance (invention product 12). The tyrosine of each invention product is determined according to the above method. The enzyme inhibitory activity was measured by using nouvelle under reduced pressure (Comparative product 2). The results are shown in Table 2. Compared with the control, the present invention was confirmed to have potent tyrosinase inhibitory activity. In particular, when nouveiie is used as a solvent, the longer the storage period is 316704D01 201242607 Table 2 Tested plant glutaminase inhibitory activity IC5〇 ( // g/ml) Invention article 7 British cockroach extract 411 Invention product 8 Storage at room temperature 7 Year 482 Inventive product 9 Storage at room temperature 1 Year 413 Invention product 10 Storage at room temperature for 15 years 228 ' Invention product 11 Storage at room temperature for 20 years 97 Invention product 12 Santo Dolly optimal (Registry 榡) 109 Reference 2 nouvelle敖, deer-----B, your mouth is more than 10000. Compared with the control, the products of the present invention are confirmed to have strong tyrosinase inhibitory activity. In particular, when n〇uvelle is used as a solvent, the longer the storage period, the stronger the effect. From the above, it is shown that the whitening effect of the product of the present invention is strong, and in particular, the longer the shelf life, the stronger the whitening effect. These products are prepared by using an aqueous solution of ethanol as a solvent and a method for producing a white wine which is rich in dietary experience, so that a whitening agent having a high safety for oral administration can be provided. Example 3 The in vivo inhibition of melanin production was evaluated using the inventive article 6. The above-mentioned inventive product 6 (i.e., Santo Dolly Yamazaki (registered trademark) 12 years) was used for the substance to be inspected. Namely, 'Sandori whisky Yamazaki (registered trademark) was dried under reduced pressure for 12 years, and used at a final concentration of 1 〇〇//g/ml. 316704D01 201242607 The amount of melanin in the cells was measured by the following method, and 4x1 G4 B16 melanoma cells were pre-cultured in 6Qmm plastic f culture phoenix. The test substance was added after 24 hours of preculture. After culturing the cells for 3 days in the presence of the test substance, the cells were washed with PBS, and 1N of sodium hydroxide was added thereto and dissolved by heating. The absorbance c at 4 ° () nm of the culture solution was measured. The absorbance C is proportional to the amount of melanin. Regarding the reference product, after the lion was prepared without adding the test material in the above reaction system, the absorbance D at 47 〇 nm was measured, and the fine _ melanin production inhibition rate was calculated by the following formula. Inhibition rate (%) = (1~C/D)xl00 and 'measure the number of cells at the same time, and investigate the sample response to the cell. The results are shown in Table 3. ~ table 3

細胞内黑色素生產量之抑制率（％) 28.5 發明製品6顯示細胞内黑色素生產量降低。又，本發明製品之細胞增殖具有與對照品相同之程度，發明製品對於細胞增殖並無影響。 ^由上述可知本發明組成物能使細胞内黑色素生產量顯著降低，並可提供安全性高之美白劑。實施例4 按照下述方法製造含有本發明溶劑萃取物之醫藥品。錠劑：放入1kg之白櫟木片於不銹鋼容器中，加入乙醇濃度為60體積％之水溶液（30L)，在60。(：下攪拌3小時。 316704D01 20 201242607 從所得萃取液除去溶劑，而得15g之白櫟萃取物（乾燥品）將該乾燥品（5g)與乳糖（49Og)及硬脂酸鎂（5g)混合’ 以單粒式製敍:機製鍵:而成直徑l〇mm，重量300mg之錠劑。顆粒劑：粉碎上述錠劑，經整粒篩選而得20至50mesh 之顯粒劑。實施例5 按照實施例4相同方法調製白櫟萃取物，以下述組成製造含有本發明之溶劑萃取物之各種飲食品。下述組成中之白櫟萃取物（乾燥品）乃實施例4所製成者。水飴： (重量份） 99. 7 0. 2 0. 05 0. 05 100 (重量份） 47. 0 49. 76 0.24 (乡且成） &梨醇粉末香料白機萃取物（乾燥品）醇種晶 — 總量糖菜： (級成）砂糙水飴香料水總量 316704D01 100 21 201242607 含錠： (重量份） 6 73 0. 05 17 0. 1 3. 55 (組成）阿拉伯膠葡萄糖白櫟萃取物（乾燥品）填酸二鉀填酸一斜乳糖香料硬脂酸鎂總量 100 口香糖： (組成）（重量份）口香糖膠 20 碳酸鈣 2 甜菊精 0.1 白櫟萃取物（乾燥品） 0.05 乳糖 76.85 香料_1 總量 100 牛奶糖： (組成）（重量份）粒狀糖 32.0 水始 20.0 316704D01 22 201242607 粉乳 40. 0 硬化油 4. 0 食鹽 0. 6 香料 0. 02 水 3. 22 白櫟萃取物（乾燥品） 0. 16 總量 100 果;東（咖嗓果;東）： (組成） (重量份）粒狀糖 15. 0 明膠 1. 0 咖啡萃取物 5. 0 水 78. 93 白櫟萃取物（乾燥品） 0.07 總量 100 冰漠淋· (組成） (重量份）鮮奶油（45%脂肪） 33.8 脫脂奶粉 11. 0 粒狀糖 14.8 加糖卵黃 0. 3 香草萃取物 0. 1 水 39. 93 白櫟萃取物（乾燥品） 0. 07 316704D01 23 201242607 總量 100 卡士達布丁： (組成） (重量份）牛奶 47. 51 全蛋 31. 9 南級白糖 17. 1 水 3.4 白櫟萃取物（乾燥品） 0. 09 總量 100 水羊羹： (組成） (重量份）紅豆銘 24.8 瓊脂粉末 0. 3 食鹽 0. 1 南級白糖 24.9 白櫟萃取物（乾燥品） 0. 1 水 49.8 總量 100 果汁飲料： (組成） (重量份）冷凍濃縮溫州蜜柑果汁 5 果糖葡萄糖液糖 11 枸櫞酸 0.2 L-抗壞血酸 0.02 316704D01 24 201242607 白櫟萃取物（乾燥品）香料 0. 05 0. 2 色素 0. 1 水 83.43 總量碳酸飲料： 100 (組成） (重量份）粒狀糖 8. 0 濃縮擰檬果汁 1. 0 L-抗壞血酸 0. 10 枸櫞酸 0. 06 枸櫞酸鈉 0. 05 色素 0. 05 香料 0. 15 碳酸水 90. 55 白櫟萃取物（乾燥品） 0. 04 總量乳酸菌飲料： 100 (組成） (重量份）含乳固形物21%發酵乳 14. 76 果糖葡萄糖液糖 13. 31 果膠枸櫞酸香料 0· 5 0. 08 0. 15 0. 08 0. 15 316704D01 25 201242607 水白櫟萃取物（乾燥品）總量咖啡飲料： (組成）粒狀糖脫脂奶粉焦糖咖啡萃取物香料聚甘油脂肪酸酯食鹽水白櫟萃取物（乾燥品） 71. 14 0. 06 100 (重量份） 05 05 84. 56 0. 04 總量 100 酒精飲料： (組成） (重量份） 50體積％乙醇 32 砂糖 8.4 果汁 2.4 白櫟萃取物（乾燥品） 0.2 精製水 57. 0 實施例6 按照實施例4相同方法調製白櫟萃取物，以下列所示 316704D01 26 201242607 ，組成製造含有本發明溶劑萃取物之各種香粧品。下列組成中之白櫟萃取物（乾燥品）乃實施例4中所製得者。牙粉劑： (重量份） 42 18 (組成）磷酸氫鈣甘油 0. 09 0. 005 0. 05 1 36. 755 角叉菜膠硫酸月桂酯鈉糖精鈉對羥基苯曱酸丁酯白櫟萃取物（乾燥品）香料水總量 100 洗口液： (組成）（重量份）硫酸月桂酯鈉 0.8 甘油 7 山梨醇 5 乙醇 15 白櫟萃取物（乾燥品） 0. 05 1-薄荷醇 0.05 香料 0.04 糖精納 0. 1 316704D01 27 201242607 ^_ 總量柔軟香粧品（弱酸性）： (組成）甘油丙二醇透明質酸鈉白櫟萃取物（乾燥品）聚氧化乙烯山梨糖酐單月桂酸酯 (20 E. 0.) 聚氧化乙烯月桂基醚（20 E.O.) 乙醇香料染料防腐劑紫外光吸收劑精製水潤膚霜： (組成）蜜蠟硬脂醇硬脂酸角鯊烧自身乳化型丙二醇單硬脂酸酯 71. 96 100 (重量份）Inhibition rate of intracellular melanin production (%) 28.5 Inventive product 6 showed a decrease in intracellular melanin production. Further, the cell proliferation of the product of the present invention is the same as that of the control, and the inventive article has no effect on cell proliferation. From the above, it is understood that the composition of the present invention can significantly reduce the amount of melanin production in cells and provide a highly safe whitening agent. Example 4 A pharmaceutical product containing the solvent extract of the present invention was produced by the following method. Tablets: 1 kg of white eucalyptus chips were placed in a stainless steel container, and an aqueous solution (30 L) having an ethanol concentration of 60 vol% was added at 60. (: stirring for 3 hours. 316704D01 20 201242607 The solvent was removed from the obtained extract to obtain 15 g of white peony extract (dried product). The dried product (5 g) was mixed with lactose (49 Og) and magnesium stearate (5 g). 'Single-grain type: mechanism key: a lozenge with a diameter of l〇mm and a weight of 300mg. Granules: The above-mentioned tablets are pulverized and sieved to obtain 20 to 50 mesh granules. Example 5 In the same manner as in Example 4, a white peony extract was prepared, and various foods and drinks containing the solvent extract of the present invention were produced in the following composition. The extract of peony (dried product) in the following composition was prepared in Example 4. : (parts by weight) 99. 7 0. 2 0. 05 0. 05 100 (parts by weight) 47. 0 49. 76 0.24 (Hometown) & Pear Powder Powder White Extract (Dry) Alcohol Crystal - Total amount of sugar: (Grade) Total amount of ground water and fragrant water 316704D01 100 21 201242607 Ingot: (parts by weight) 6 73 0. 05 17 0. 1 3. 55 (Composition) Gum arabic glucose extract (dry product) filled with potassium dipotassium acid, lycopene, spice, magnesium stearate, 100 Chewing gum: (composition) (parts by weight) Chewing gum 20 Calcium carbonate 2 Stevia 0.1 White peony extract (dry) 0.05 Lactose 76.85 Spice _1 Total 100 Milk sugar: (composition) (parts by weight) Granulated sugar 32.0 Water start 20.0 316704D01 22 201242607 Powdered milk 40. 0 Hardened oil 4. 0 Salt 0. 6 Spice 0. 02 Water 3. 22 White peony extract (dry product) 0. 16 Total 100 fruit; East (Curry fruit; East ): (composition) (parts by weight) granulated sugar 15. 0 gelatin 1. 0 coffee extract 5. 0 water 78. 93 white peony extract (dry product) 0.07 total amount 100 ice desert (composition) (weight份) whipped cream (45% fat) 33.8 skim milk powder 11. 0 granulated sugar 14.8 sugared yolk 0. 3 vanilla extract 0. 1 water 39. 93 white peony extract (dry product) 0. 07 316704D01 23 201242607 total 100 kstar pudding: (composition) (parts by weight) milk 47. 51 whole egg 31. 9 southern sugar 17.1 water 3.4 white peony extract (dry product) 0. 09 total 100 water sheep: (composition) (重量份) 红豆铭 24.8 Agar powder 0. 3 Salt 0. 1 Southern sugar 24.9 White peony extract (dry product) 0. 1 Water 49.8 Total 100 Juice drink: (composition) (parts by weight) Frozen concentrated Wenzhou mandarin juice 5 Fructose glucose liquid sugar 11 citric acid 0.2 L-ascorbic acid 0.02 316704D01 24 201242607 White peony extract (dry product) Spice 0. 05 0. 2 Pigment 0. 1 Water 83.43 Total carbonated beverage: 100 (composition) (parts by weight) Granulated sugar 8. 0 concentrated lemon juice 1. 0 L-ascorbic acid 0. 10 decanoic acid 0. 06 sodium citrate 0. 05 pigment 0. 05 spice 0. 15 carbonated water 90. 55 white peony extract (dry product) 0. 04 total lactic acid bacteria drink: 100 ( Composition) (parts by weight) containing milk solids 21% fermented milk 14. 76 fructose glucose liquid sugar 13. 31 pectin tannic acid spice 0· 5 0. 08 0. 15 0. 08 0. 15 316704D01 25 201242607 water white栎 extract (dry product) Total coffee drink: (composition) granulated sugar skim milk powder caramel coffee extract flavor polyglycerin fatty acid ester salt water white peony extract (dry product) 71. 14 0. 06 100 (weight Share) 05 05 84. 56 0. 04 Total 10 0 Alcoholic beverage: (composition) (parts by weight) 50% by volume of ethanol 32 Sugar 8.4 Juice 2.4 White peony extract (dry product) 0.2 Refined water 57. 0 Example 6 The white peony extract was prepared in the same manner as in Example 4, and the following The column shows 316704D01 26 201242607, which constitutes a variety of cosmetic products containing the solvent extract of the present invention. The extract of the white peony (dried product) of the following composition was prepared in Example 4. Tooth powder: (parts by weight) 42 18 (composition) Calcium hydrogen phosphate glycerol 0. 09 0. 005 0. 05 1 36. 755 Carrageenan sodium lauryl sulfate sodium saccharin sodium p-hydroxybenzoate citrate extract (Dry product) Total amount of perfume water 100 Washing liquid: (composition) (parts by weight) Sodium lauryl sulfate 0.8 Glycerin 7 Sorbitol 5 Ethanol 15 White peony extract (dry product) 0. 05 1-Menthol 0.05 Fragrance 0.04 Saccharin sodium 0. 1 316704D01 27 201242607 ^_ Total soft cosmetic (weakly acidic): (composition) Glycerol propylene glycol sodium hyaluronate white peony extract (dry product) Polyoxyethylene sorbitan monolaurate (20 E 0.) Polyoxyethylene lauryl ether (20 EO) Ethanol perfume dye preservative UV light absorbent refined water moisturizer: (composition) beeswax stearyl stearic acid sharks burn self-emulsified propylene glycol monostearyl Acid ester 71. 96 100 (parts by weight)

10. 0 0. 1 微量微量微量 78. 75 (重量份）10. 0 0. 1 trace amount trace amount 78. 75 (parts by weight)

316704D01 28 201242607 1 聚氧化乙烯鯨蠟醚（20 E. 0.) 香料抗氧化劑防腐劑丙二醇甘油透明質酸鈉白櫟萃取物（乾燥品）三乙醇胺精製水潤膚洗劑： (組成）硬脂酸録鐵醇凡士林羊毛脂醇液態石蠟聚氧化乙烯單油酸酯（10 E. 0.) 香料抗氧化劑防腐劑丙二醇甘油透明質酸鈉316704D01 28 201242607 1 Polyethylene oxide cetyl ether (20 E. 0.) Perfume antioxidant preservative propylene glycol glycerin sodium hyaluronate white peony extract (dry product) Triethanolamine refined water emollient lotion: (composition) hard fat Acidic iron alcohol Vaseline lanolin alcohol liquid paraffin polyoxyethylene monooleate (10 E. 0.) perfume antioxidant preservative propylene glycol glycerin sodium hyaluronate

微量微量Trace amount

(重量份） 10 微量微量 4. 8 3. 0 0. 1 316704D01 29 201242607 白櫟萃取物（乾燥品）三乙醇胺精製水乳液狀粉底： (組成）硬脂酸丙二醇單硬脂酸酯乙二醇錄躐醇•硬脂醇混合物液狀羊毛脂液態石蠟肉豆蔻酸異丙酯對羥基苯曱酸丙酯精製水羥曱基纖維素鈉膨潤土丙二醇透明質酸鈉白櫟萃取物（乾燥品）三乙醇胺對羥基苯曱酸曱酯氧化鈦滑石色素 70. 0 (重量份） 2.4(Parts by weight) 10 Trace amount 4. 8 3. 0 0. 1 316704D01 29 201242607 White peony extract (dry product) Triethanolamine refined water emulsion foundation: (composition) Stearic acid propylene glycol monostearate ethylene glycol Recording sterol and stearyl alcohol mixture liquid lanolin liquid paraffin isopropyl myristate isopropyl p-hydroxybenzoate propyl ester purified water hydroxy decyl cellulose sodium bentonite propylene glycol sodium hyaluronate white peony extract (dry product) three Ethanolamine p-hydroxybenzoic acid decyl ester titanium oxide talc pigment 70. 0 (parts by weight) 2.4

微量 8.Trace 8.

微量 316704D01 30 I201242607 ，香料生髮水： (組成）乙醇曰本當藥萃取物維生素E L-薄荷醇甘草精白櫟萃取物（乾燥品）水揚酸甘油香料精製水洗髮劑： (組成）烧基驗硫酸納（AES-Na) 月桂酸二乙醇醯胺丙二醇白櫟萃取物（乾燥品）防腐劑色素香料精製水微量 (重量份） 70. 0 微量 28. 0 (重量份） 16. 0 微量微量微量 78. 0 潤髮劑： 316704D01 31 201242607 (組成） (重量份）氣化硬脂基二曱基苯曱銨 1.4 硬脂醇 0.6 甘油單硬脂酸酯 1.5 食鹽 0.1 白櫟萃取物（乾燥品） 0.1 精製水 96.3 產業上之利用性本發明乃關於含有殼斗科櫟屬植物之溶劑萃取物而具有美白作用之飲食品、香粧品或醫藥品。【圖式簡單說明】無。【主要元件符號說明】無。 316704D01 32Trace 316704D01 30 I201242607 , Perfumery hair lotion: (composition) Ethanol 曰 Bento drug extract Vitamin E L-menthol licorice extract (dry product) Water glycerin fragrance refined water shampoo: (composition) Sodium sulphate (AES-Na) lauric acid diethanol guanamine propylene glycol white peony extract (dry product) preservative pigment flavor refined water trace (parts by weight) 70. 0 trace 28. 0 (parts by weight) 16. 0 trace micro trace 78. 0 conditioner: 316704D01 31 201242607 (composition) (parts by weight) gasified stearyl dimercaptobenzamine 1.4 stearyl alcohol 0.6 glyceryl monostearate 1.5 salt 0.1 white peony extract (dry product) 0.1 Refined Water 96.3 Industrial Applicability The present invention relates to a food or drink, a cosmetic, or a pharmaceutical product which has a whitening action by a solvent extract of the genus Fagaceae. [Simple description of the diagram] None. [Main component symbol description] None. 316704D01 32

Claims

201242607 VII 1. ‘Application for patent: A whitening agent' is characterized by the solvent extraction of the ancient or British cockroach. The white machine = 6060 to 7. The aqueous solution of the sputum is used to remove the bark from the trunk and the main branch. Two 1fciU item 1 of the self-agent, wherein the extract is extracted, from the liquid concentrate or the dried extract of the extract. :!2 The whitening agent of item 1 of the range of benefits, wherein the genus Fagaceae is in the form of a casks of whiskey or brandy made up of wood, wood, and brandy. 4. For example, the patent for the beta month is the whitening agent of the first item, wherein the solvent is obtained by steaming the alcohol. • The whitening agent of claim 4, wherein the solvent extract is obtained by contacting the ethanol-containing material with oak barrels in oak barrels. 6. For example, the beauty agent of item 5 of the U profit range has a contact period of more than half a year. 7. The whitening cloth of the first paragraph of the patent application is any one of whisky, brandy, or a concentrate or a dried product thereof. 8. A whitening agent according to any one of the claims to the seventh to seventh items, which is a food or drink, a cosmetic or a pharmaceutical. 9. For the whitening agent in the eighth paragraph of the patent scope, it is a cosmetic product for external use or a pharmaceutical product for use outside 316704D01 1 201242607. Ιο· If you apply for the whitening agent in item 8 of the patent scope, it is a food or beverage, oral cosmetic or oral medicine. An additive or a formulation for use in a food or beverage, a cosmetic or a pharmaceutical, characterized by containing a solvent extract of a white peony or a British cockroach belonging to the genus Fagaceae, the solvent being 60 to 70% by volume The aqueous solution of ethanol is used as the raw material of the genus Fagaceae, and the part of the bark is removed from the trunk and the main branch; only the case where the heartwood is removed is the wood piece. 12. A melanin production inhibitor characterized by containing a solvent extract of a white peony or a British cockroach belonging to the genus Fagaceae, and the solvent is an aqueous solution of 60 to 70% by volume of the solvent, as the aforementioned Fagaceae The part used for the raw material of the genus is the heart material from which the bark is removed from the trunk and the main branch; however, the case where the shape of the heartwood is the wood piece is excluded. 13. The use of a solvent extract of a heart machine of the bark and the main branch to remove the bark of the bark of the genus Fagaceae, for use as a whitening agent, wherein the solvent is 60 to 70 bodies. An aqueous solution of ethanol; only the case where the form of the heartwood is excluded from wood chips. 316704D01 2 201242607 IV. Designation of Representative Representatives (1) The representative representative of the case is: The case has no drawing. (2) A brief description of the symbol of the representative figure: None. 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: There is no chemical formula in this case. 316704D01 2