201247197 六、發明說明： (相關申請） 本案係主張2011年4月12曰提出申請之日本國發明 專利申請2011-88317號之優先權，並於此援用其内容。 【發明所屬之技術領域】 本發明係關於美白劑及黑色素生成抑制劑’特別係關 於其有效成分。 【先前技術】 皮膚之暗沉/雀斑等色素沉著，被認為係由於荷爾蒙 之異常或紫外線、皮膚局部的炎症而過剩地形成黑色素， 且該黑色素沉著於皮膚内所致。皮膚之色素沉著原因之該 黑色素，係由在表皮基底層所具有之色素細胞（黑色素細胞 (melanocyte))内被稱為黑素體（meian0some)的胞器所生 成’而所生成之黑色素會進入周圍的角質細胞 (keratinocyte) ° 作為如上述色素沉著之預防/改善方法，係使用具有 美白作用之物質’亦即，主要係使用抑制黑色素生成之物 質°作為色素沉著之預防/改善方法，已知例如大量經口投 予維生素C之方法、注射麩胱甘肽（glutathione)等方法； 或者是將麴酸、維生素C及其衍生物、半胱胺酸等以軟膏、 乳霜、乳劑（lotion)等形態局部性地塗佈於皮膚之方法等。 另一方面，茶腹安酸（chafuroside)係可藉由從烏龍 茶等茶萃取而分離之化合物。該茶腹安酸對於過敏性疾病 係屬有效，而已知以高比例包含該茶腹安酸的茶葉之取得 324104 3 201247197 方法（專利文獻1)。惟，並非關於茶腹安酸B(chafuroside B)之美白效果、黑色素生成抑制效果之報告。 [先前技術文獻] [專利文獻] [專利文獻1]日本特開2009-131161號公報 【發明内容】 (發明欲解決之課題） 本發明係有鑑於前述先前技術而施行者，其欲解決之 課題在於提供一種具有優異的美白作用、黑色素生成抑制 作用，而有用於作為美白劑及黑色素生成抑制劑之化合物。 (解決課題之手段） 本發明者等為了解決前述課題而進行精心研究，結果 係發現茶腹安酸B係具有優異的美白作用及黑色素生成抑 制作用，遂完成本發明。 亦即，本發明之美白劑係含有茶腹安酸B。 本發明之黑色素生成抑制劑係含有茶腹安酸B。 本發明之黑色素生成抑制方法，係將包含有效量的茶 腹安酸B之組成物經口投予。 此外，本發明之黑色素生成抑制方法，係將包含有效 量的茶腹安酸B之組成物塗佈於皮膚。 前述黑色素生成抑制方法中，茶腹安酸B之功能以作 為美白劑較佳。 一種茶腹安酸B之用途，其係作為本發明之含有茶腹 安酸B的美白劑之製造中的有效成分。 324104 4 201247197 於前述用途中，前述茶腹安酸B以抑制黑色素生成較 佳。 (發明之效果） 本發明之美白劑及黑色素生成抑制劑，係含有茶腹安 酸B，可提供一種美白作用、黑色素生成抑制作用優異之 製劑。 【實施方式】 本發明之美白劑及黑色素生成抑制劑係含有茶腹安 酸B者。茶腹安酸B係下述式（I)所示之黃酮C(fl avoneC) 配糖體。201247197 VI. INSTRUCTIONS: (Related application) This application claims the priority of Japanese Patent Application No. 2011-88317 filed on Apr. 12, 2011, the entire disclosure of which is incorporated herein. TECHNICAL FIELD OF THE INVENTION The present invention relates to a whitening agent and a melanin production inhibitor' in particular to its active ingredient. [Prior Art] Pigmentation such as dullness of the skin/freckles is thought to be caused by excessive formation of melanin due to abnormalities of hormones or ultraviolet rays, local inflammation of the skin, and the melanin is deposited in the skin. The melanin, which is caused by the pigmentation of the skin, is produced by a cell called a mesensome (melanocyte) in the basal layer of the epidermis, and the melanin produced is entered. Peripheral keratinocyte (keratinocyte) ° As a method for preventing/improving pigmentation as described above, a substance having a whitening effect is used, that is, a substance which inhibits melanin production is mainly used as a method for preventing/improving pigmentation, and is known. For example, a large amount of oral administration of vitamin C, injection of glutathione (glutathione) or the like; or citrate, vitamin C and its derivatives, cysteine, etc. as ointment, cream, lotion (lotion) A method in which the form is locally applied to the skin or the like. On the other hand, chafuroside is a compound which can be isolated by extraction from tea such as oolong tea. The tea amphoteric acid is effective for an allergic disease, and a method of obtaining a tea leaf containing the tea amphoteric acid in a high ratio is known as 324104 3 201247197 (Patent Document 1). However, it is not a report on the whitening effect of the chafuroside B and the inhibitory effect on melanin production. [PRIOR ART DOCUMENT] [Patent Document 1] [Patent Document 1] JP-A-2009-131161 SUMMARY OF INVENTION [Problem to be Solved by the Invention] The present invention has been made in view of the above prior art, and the problem to be solved is It is to provide a compound which has an excellent whitening action and melanin production inhibitory action, and is useful as a whitening agent and a melanin production inhibitor. (Means for Solving the Problems) The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems. As a result, it has been found that the tea buckwheat acid B system has an excellent whitening action and melanin production suppressing action, and has completed the present invention. That is, the whitening agent of the present invention contains tea belly acid B. The melanin production inhibitor of the present invention contains Chabian An acid B. The method for inhibiting melanin production according to the present invention is to orally administer a composition comprising an effective amount of catechin B. Further, the melanin production inhibiting method of the present invention is a method comprising applying an effective amount of a composition of Cha Vinic Acid B to the skin. In the above method for inhibiting melanin production, the function of the tea amphoteric acid B is preferred as a whitening agent. Use of a tea belly acid B as an active ingredient in the manufacture of a whitening agent containing tea belly acid B of the present invention. 324104 4 201247197 In the foregoing use, the aforementioned tea amphoteric acid B is preferred to inhibit melanin production. (Effects of the Invention) The whitening agent and the melanin production inhibitor of the present invention contain a tea belly acid B, and provide a preparation excellent in whitening action and melanin production inhibitory action. [Embodiment] The whitening agent and the melanin production inhibitor of the present invention contain a tea belly acid B. The tea amphoteric acid B is a flavonoid C (fl avone C) glycoside represented by the following formula (I).
茶腹安酸B之製造方法並無特別限定，可使用以公知 方法所合成之合成品，亦可藉由公知之精製方法從綠茶、 焙茶、紅茶、烏龍茶等茶葉進行分離。 將包含美白劑及黑色素生成抑制劑的有效成分之茶 腹安酸B之組成物進行經口投予時，以投予有效量的茶腹 安酸B為宜。茶腹安酸B係以每1日投予0. 001mg/kgb. w. 324104 5 201247197 以上為且A外’以每i日投予lmg/kgb.^以上為特佳。 本毛月之美白劑及黑色素生成抑制劑，亦可調配於美 白用飲料或疋美白用食品。美白用飲料或美白用食品中， 除有效成刀之禮安㈣之外，可視所需*任意地選擇並 調配添加劑。作為添加劑，可列舉賦形劑、呈味劑、著色 劑、保存劑、增賴、紋劑、膠化劑、抗氧化劑、功能 性原料等。 作為功能性原料，可列舉各種維生素類、泛酸、葉酸、 生物素（biotin)、鋅、鈣、鎂、胺基酸、寡糖、蜂膠 (propolis)、蜂王漿（r〇yal jeUy)、EpA、DHA、辅酶 QliKcoenzpieQ-lO)、軟骨素（ch〇ndr〇itin)、乳酸菌、乳 鐵素（lactoferrin)、異黃酮、乾果李（prune)、幾丁質 (chitin)、幾丁聚糖（chit〇san)、葡萄糖胺等。 作為賦形劑，只要為所期望劑型時之一般可使用者即 無限定，可列舉例如，如微粒子二氧化矽之粉末類；蔗糖 脂肪酸酯、結晶纖維素/羧曱基纖維素鈉、磷酸氫鈣；小麥 殿粉、米澱粉、玉米殿粉、馬鈴薯殿粉、糊精、環糊精等 殿粉類；結晶纖維素類；乳糖、葡萄糖、砂糖、還原麥芽 糖、澱粉糖漿、低聚果糖（丨1*11〇1；〇-〇1丨运〇58〇0^]：丨(16)、乳 化寡糠等糖類；山梨糖醇、赤藻糖醇、木糖醇（xylitol)、 乳糖醇、甘露糖醇等糖醇類等。 作為呈味劑，可列舉果汁萃取物之文旦萃取物、荔枝 萃取物、頻果果汁、掛橘果汁、柚子萃取物、桃果風味（peach flavor)、梅子風味；甘味劑之醋磺内酯鉀（acesul fame K); 324104 6 201247197 赤藻糖醇、寡糖類、甘露糖、木糖醇、異性化糖類、茶成 77 之表 >、烏龍命、大花紫薇（Lagerstroemia speciosa) $、杜仲茶、鐵觀音茶、薏苡茶、七葉膽茶、菰茶、昆布 茶、優酷風味等。 著色劑、保存劑、增黏劑、安定劑、膠化劑、抗氧化 劑’係可適宜選擇用於飲食品之公知者。 本發明之美白劑及黑色素生成抑制劑的形態，可為安 瓿（ampule)、膠囊、丸劑、錠劑、粉末、顆粒、固態、液 體、凝膠或是氣泡、乳霜等任意形態。 具體而言，可列舉例如，美容/健康飲料或是食品、 邊藥α〇，西式點心類、和式點心類、口香糖、糖果、牛奶 糖等-般點心類；果實果汁等—般清涼飲料水；魚板、竹 輪等加工水產練製品；香腸、火腿等畜產製品；生麵、熟 麵、蕎麥麵等麵類；調味醬（sauce)、醬油、醬料（tare)、 砂糖、蜂蜜、澱粉糖粉、澱粉糖漿等調味料；咖哩粉、芥 子粉、胡椒粉等香辛料；果醬、果皮醬（marmalade)、巧克 力醬，起司、奶油、優格等乳製品等。較佳可列舉為了可 以良好效率攝取而經口投予之美容/健康飲料或美容/健康 食品等。 此外’該等係可藉由以往公知的方法製造。 又’本發明之美白劑及黑色素生成抑制劑，亦可期待 經皮吸收之效果而調配於皮膚外用劑等組成物。皮膚外用 劑之形態可列舉化妝料、貼附劑、醫藥品等。 於皮膚外用劑，除了有效成分茶腹安酸B以外，可視 324104 7 201247197 所需而適宜調配一般可使用於化妝料或醫藥品等皮膚外用 劑之成分，例如，保濕劑、抗氧化劑、油性成分、紫外線 吸收劑、界面活性劑、增黏劑、醇類、粉末成分、色劑、 水性成分、水、各種皮膚營養劑等。 於包含本發明之美白劑的皮膚外用劑中，以調配有效 量之茶腹安酸B較合適。皮膚外用劑總量中，茶腹安酸B 的調配量係以0. 0 01至5. 0質量％為特別合適。調配量若過 少，則無法充分地發揮美白效果，而即使調配量為過多， 亦無法達到相應的明顯提升效果，故為不佳。 (實施例） 關於本發明’係列舉以下實施例以進一步詳述，惟本 發明並不限定於該等。 於以下試驗中所使用的動物，係使用DBA/2小鼠雄性 (CHARLES RIVER LABORATORIES JAPAN 股份有限公司）。取 得5週大的小鼠，馴化飼育1週後使用。 此外’讓小鼠自由地攝取滅菌蒸餾水及飼料AIN-93G (曰本農產工業股份有限公司）。 牡弃素（vitexin)、異牡荊素（isovitexin)係使用 市售品（SIGMA-ALDRICH股份有限公司），茶腹安酸B係以 公知之方法（J. Agric. f00(1 Chem. 2009，57，6779-6786) 從茶分離者。然後，使用上述動物，藉由下述試驗方法進 行黑色素細胞活化抑制試驗。 又’牡々素、異牡荊素分別係與茶腹安酸B同樣地包 含於茶中之類黃蜩（flavonoid)。 324104 8 201247197 H素&胞Μ抑制試驗方法 ϊ 内對小鼠將包含牡荆素或異牡荆素或是茶腹 安酸Bdmg/kgb.w.)之媒質強制經口投予至胃^於投予 後進行照射照射量l2〇mJ之中波長紫外線（_)。同樣地 對對照組（未照射群組）及對照組（ϋν照射群組）投予媒 質。又，各群組分別係以8隻小鼠進行試驗。 本°式驗中’媒質及其投予用量，係以0. 5w/v%甲基纖 維素400溶液，5mL/kgb. w.進行。 於第10日採取皮膚，進行DOPA反應。於顯微鏡觀察 下，异出單位面積之D0pa陽性黑色素細胞數。 —結果係示於第1圖。又，圖中之*係藉由司徒頓t檢 疋（Student t test)(顯著水準 *ρ<〇〇5，**ρ<〇·〇ι) 進行統計處理時，表示可確認到相對於對照組⑽照射 組）之顯著差者。 r “依據第1圖’具有與茶腹安酸請似結構的類黃網之 牡莉素雖有抑制黑色素細胞數的增加之傾向，惟並 ，抑制。此外，具有與茶腹安酸八類似結構的類之 牡刑素，係顯著地抑制了黑色素細胞數的增加。、.之異 惟，令人驚訝的是，茶腹安酸B非常顯 色素細胞數的增加。 也抑制了黑 其次，本發明者等以茶腹安酸A及茶腹K & 樣，以與上述試驗方法相同的方式進行黑色=馱B作為試 制試驗。結果係示於第2圖。 、’、細皰活化抑 依據第2圖，確認到藉由照射uv，D卯 324104 9 陽性黑色素 201247197 細胞數係顯著增加（UV照射群組）。茶腹安酸A及茶腹安酸 B係顯著地抑制了黑色素細胞數的增加。惟明瞭到，比起 茶腹安酸A，茶腹安酸B係更為顯著地抑制了黑色素細胞 數的增加。 因此，本發明之美白劑及黑色素生成抑制劑之特徵係 含有茶腹安酸B者。 以下，列舉本發明之美白劑及黑色素生成抑制劑的茶 腹安酸B之調配例。而本發明並不限定於此。 240 mg 40 150 270 350 36 36 30 24 24 0.01質量％ 調配例1顆粒 茶腹安酸B 蓮胚芽萃取物 維生素C 大豆異黃酮 還原乳糖 大豆寡糖 赤藻糖醇 糊精 香料 擰檬酸 20. 0 調配例2乳液 茶腹安酸B 微晶蠟 蜜蠟 羊毛脂 324104 10 201247197 液體石蠟 角鯊烧 山梨醇酐倍半油酸酯 Ρ0Ε ( 2 0 )山梨醇酐單油酸酉旨 丙二醇 亞硫酸氩鈉 對羥基苯甲酸乙酯 10. 0 5 01 香料 適量 精製水 餘量 【圖式簡單說明】 第1圖係驗証牡荊素、異牡荊素、茶腹安酸B對於UVB 表皮黑色素細胞活化的效果之圖。 第2圖係表示茶腹安酸A及茶腹安酸B對於UVB表皮 黑色素細胞活化的效果之圖。 【主要元件符號說明】 無 324104 11The method for producing the tea amphoteric acid B is not particularly limited, and a synthetic product synthesized by a known method may be used, and it may be separated from tea leaves such as green tea, roasted tea, black tea, and oolong tea by a known purification method. When the composition of the tea acenamic acid B containing the active ingredient of the whitening agent and the melanin production inhibitor is administered orally, it is preferred to administer an effective amount of the tea succinic acid B. The tea amphoteric acid B is administered at a ratio of 0.001 mg/kgb. w. 324104 5 201247197 or more and A outside is administered at a rate of 1 mg/kgb. This Maoyue whitening agent and melanin production inhibitor can also be formulated in whitening or whitening foods. In the whitening beverage or whitening food, in addition to the effective knife-making ceremony (4), the additive can be arbitrarily selected and formulated according to the required *. Examples of the additive include an excipient, a flavoring agent, a coloring agent, a preservative, a sizing agent, a sizing agent, a gelling agent, an antioxidant, and a functional raw material. As a functional raw material, various vitamins, pantothenic acid, folic acid, biotin, zinc, calcium, magnesium, amino acid, oligosaccharide, propolis, royal jelly (r〇yal jeUy), EpA, DHA can be cited. Coenzyme QliKcoenzpieQ-lO), chondroitin (ch〇ndr〇itin), lactic acid bacteria, lactoferrin, isoflavones, prune, chitin, chitin (chit〇san) ), glucosamine, and the like. The excipient is generally not limited as long as it is a desired dosage form, and examples thereof include powders such as fine particle cerium oxide; sucrose fatty acid ester, crystalline cellulose/carboxymethyl cellulose sodium, and phosphoric acid. Hydrogen calcium; wheat house powder, rice starch, corn house powder, potato house powder, dextrin, cyclodextrin, etc.; crystalline cellulose; lactose, glucose, sugar, reduced maltose, starch syrup, oligofructose (丨1*11〇1;〇-〇1丨丨〇58〇0^]: 丨(16), emulsified oligosaccharides and other sugars; sorbitol, erythritol, xylitol, lactitol, Examples of the flavoring agent include a dendritic extract of a fruit juice extract, a lychee extract, a frequency fruit juice, a hanging orange juice, a grapefruit extract, a peach flavor, and a plum flavor; Acesulfame lactone potassium (acesul fame K); 324104 6 201247197 erythritol, oligosaccharides, mannose, xylitol, heterosexual sugars, tea into 77>, oolong life, large flower Lagerstroemia speciosa $, Eucommia tea, Tieguanyin tea Tea, espresso, tea, kelp, Youku, etc. Colorants, preservatives, tackifiers, stabilizers, gelling agents, antioxidants are suitable for use in food and beverage products. The form of the whitening agent and the melanin production inhibitor of the present invention may be in the form of an ampoule, a capsule, a pill, a tablet, a powder, a granule, a solid, a liquid, a gel, or a bubble or a cream. For example, a beauty/health drink or a food, a side-effect medicine, a western-style snack, a dim sum, a chewing gum, a candy, a milk candy, and the like; a fruit juice; a refreshing drink water; a fish plate , bamboo wheels and other processed aquatic products; sausages, ham and other livestock products; noodles, cooked noodles, soba noodles and other noodles; sauce (sauce), soy sauce, sauce (tare), sugar, honey, starch powder, starch Seasonings such as syrup; curry powder, mustard powder, pepper and other spices; jam, marmalade, chocolate sauce, cheese, cream, yogurt, etc. It is better to be listed as good A beauty/health drink or a beauty/health food which is administered orally, etc. Further, these can be produced by a conventionally known method. Further, the whitening agent and the melanin production inhibitor of the present invention can also be expected to be percutaneously The composition of the external preparation for skin may be formulated as a cosmetic, a patch, a pharmaceutical, etc. The external preparation for skin may be used in addition to the active ingredient, catechin B, 324104 7 201247197 It is suitable for blending with ingredients suitable for external preparations for skin such as cosmetics or pharmaceuticals, for example, moisturizers, antioxidants, oily ingredients, ultraviolet absorbers, surfactants, tackifiers, alcohols, powder ingredients, Colorants, water-based ingredients, water, various skin nutrients, etc. In the external preparation for skin containing the whitening agent of the present invention, it is preferred to formulate an effective amount of the tea belly acid B. 0质量质量为特别优选为。 The total amount of the external application of the skin, the amount of the tea amphoteric acid B is 0. 0 01 to 5.0% by mass is particularly suitable. If the amount of blending is too small, the whitening effect cannot be fully exerted, and even if the blending amount is too large, the corresponding significant lifting effect cannot be achieved, which is not preferable. (Embodiment) The following examples are described in detail in the present invention, but the present invention is not limited thereto. For the animals used in the following tests, DBA/2 mouse males (CHARLES RIVER LABORATORIES JAPAN Co., Ltd.) were used. Five-week-old mice were obtained and used after 1 week of domestication. In addition, mice were given free access to sterile distilled water and feed AIN-93G (Sakamoto Agro Industries Co., Ltd.). A commercially available product (SIGMA-ALDRICH Co., Ltd.) is used for vitexin and isovitexin, and a tea base is used in a known method (J. Agric. f00 (1 Chem. 2009, 57,6779-6786) Separation from tea. Then, using the above-mentioned animals, the melanocyte activation inhibition test was carried out by the following test method. Further, 'oyrubin and isovite are the same as the tea belly acid B, respectively. Contains flavonoids such as flavonoids. 324104 8 201247197 H- & cytosolic inhibition test method ϊ The inner mouse will contain vitexin or isovite or tea belly acid Bdmg/kgb.w .) The medium is forcibly administered orally to the stomach. After the administration, the wavelength of ultraviolet rays (_) is irradiated with an irradiation dose of l2〇mJ. Similarly, the control group (unirradiated group) and the control group (ϋν irradiation group) were administered with a medium. Further, each group was tested with 8 mice. In the present invention, the medium and the dosage thereof were carried out in a solution of 0.5 w/v% methylcellulose 400, 5 mL/kg b.w. The skin was taken on the 10th day for DOPA reaction. Under the microscope observation, the number of D0pa-positive melanocytes per unit area was different. - The results are shown in Figure 1. In addition, the * in the figure is statistically processed by the Student t test (significant level *ρ<〇〇5, **ρ<〇·〇ι), indicating that it can be confirmed relative to the control. Significant difference in group (10) irradiation group). r "Based on Fig. 1 'The lycopene-like lycopene which has a structure similar to that of the tea abalone has a tendency to suppress the increase in the number of melanocytes, but suppresses it. In addition, it has a similarity to the tea abalone. The structural class of Oysterin significantly inhibited the increase in the number of melanocytes. The heterodyne, surprisingly, the increase in the number of pigment cells in the tea amphoteric acid B. Also inhibited the blackness, The inventors of the present invention performed black = 驮B as a trial production test in the same manner as the above test method using the same as the above-mentioned test method. The results are shown in Fig. 2. ', the blister activation According to Fig. 2, it was confirmed that by irradiating uv, the number of positive melanin 201247197 cells was significantly increased (UV irradiation group). The tea amphoteric acid A and the tea amphoteric acid B system significantly inhibited the number of melanocytes. It is clear that the increase in the number of melanocytes is more pronounced than the tea amphoteric acid A. Therefore, the whitening agent and melanin production inhibitor of the present invention are characterized by containing tea. Abdominal acid B. Below, list this The formulation of the tea whitening agent B and the melanin production inhibitor B. The invention is not limited thereto. 240 mg 40 150 270 350 36 36 30 24 24 0.01% by mass Example 1 granules Lotus germ extract vitamin C soy isoflavones reduced lactose soy oligosaccharide erythritol dextrin spice lemon acid 20. 0 Formulation example 2 emulsion tea belly acid B microcrystalline wax beeswax lanolin 324104 10 201247197 liquid paraffin horn shark Saponin sesquioleate Ρ0Ε (20) sorbitan monooleate propylene glycol argon sulfite sulfite ethyl p-hydroxybenzoate 10. 0 5 01 spice amount of refined water balance [schematic description] Figure 1 is a graph showing the effect of vitexin, isovite, and catechin B on the activation of UVB epidermal melanocytes. Figure 2 shows the tea amphoteric acid A and the tea abalone B for UVB epidermal melanin. Figure of the effect of cell activation. [Main component symbol description] No 324104 11