TW202015653A - 美白劑 - Google Patents
美白劑 Download PDFInfo
- Publication number
- TW202015653A TW202015653A TW108117285A TW108117285A TW202015653A TW 202015653 A TW202015653 A TW 202015653A TW 108117285 A TW108117285 A TW 108117285A TW 108117285 A TW108117285 A TW 108117285A TW 202015653 A TW202015653 A TW 202015653A
- Authority
- TW
- Taiwan
- Prior art keywords
- acid
- phenyl
- aminomethylcyclohexylcarbonyl
- whitening
- skin
- Prior art date
Links
- 239000007854 depigmenting agent Substances 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 230000002087 whitening effect Effects 0.000 claims description 60
- 239000003795 chemical substances by application Substances 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 239000002537 cosmetic Substances 0.000 claims description 11
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- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 230000000694 effects Effects 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 2
- 125000006823 (C1-C6) acyl group Chemical group 0.000 abstract 1
- 206010040829 Skin discolouration Diseases 0.000 abstract 1
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- -1 inorganic acid salts Chemical class 0.000 description 36
- 238000003756 stirring Methods 0.000 description 16
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- 230000019612 pigmentation Effects 0.000 description 13
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- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 9
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
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- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
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Abstract
本發明係以提供具有優良美白作用的美白劑作為課題。將下述通式(1)所表示之化合物或其酸加成鹽作為美白劑的有效成分。
(式中，X表示氫原子可被甲基取代之碳數1~2的伸烷基，Y表示COOR1或CH2OR2，R1表示氫原子或可具有分支之碳數1~6的烷基，R2表示氫原子或可具有分支之碳數1~6的醯基。)
Description
本發明係關於具有優良美白作用的美白劑。
除了因紫外線曝曬所導致的曬黑以外，斑點、雀斑、肝斑、因藥劑所導致的皮膚之黑變症等之因色素沉著所導致的皮膚症狀，已知係由於色素細胞(黑色素細胞)之黑色素產生亢進後，產生的黑色素色素因轉換(turnover)異常等而在皮膚沉著所發生的。
這種與色素沉著相關的皮膚症狀由於可容易從外觀確認，而大幅影響對臉的印象。因此，對於皮膚的色素沉著之預防或改善的關心，係以具有所謂使皮膚看起來漂亮之願望者為中心而非常高，且美白劑或美白用化妝品的需求在近年正逐漸變大。
就以皮膚的色素沉著之預防或改善為目的之美白劑而言，自古已知有抗壞血酸或氫醌等，摻合此等之皮膚外用劑已被廣泛使用於皮膚的色素沉著之預防或改善用。又，近年因發生色素沉著的作用機制之闡明，而黑色素產生抑制劑、酪胺酸酶抑制劑、酪胺酸酶基因表現抑制劑、α-MSH抑制劑、抗氧化劑、黑色素細胞的樹枝狀突起伸長抑制劑、黑色素細胞之對角質細胞的黑素體輸送抑制劑等之具有與以往的美白劑不同的作用機制之美白劑的開發亦正興盛地進行中。
然而，以往的美白劑雖確認到一定的美白效果，但有不能充分滿意之情形、或在發揮美白作用之濃度下發生不希望得到的其
他作用(副反應)之情形。因此，有安全性高且發揮優良美白作用之新的成分之需求，研究開發正進行中。
西查細特(cetraxate)或其鹽亦為近年所開發之美白劑的有效成分之一，係藉由代謝而被分解為傳明酸(tranexamic acid)的化合物(專利文獻1)。傳明酸已知具有活性化黑色素細胞之前列腺素E2的產生抑制作用、與酪胺酸酶抑制作用，且發揮美白效果。西查細特已被報告除了來自其代謝物之傳明酸的美白作用，亦具有來自化合物本體之活性的美白作用。
然而，專利文獻2所記載的胺基羧酸衍生物已確認有抗潰瘍作用，且被提案作為醫藥品之用途。此外，該化合物的結構係與傳明酸部分地一致。
[專利文獻1]日本特開2008-110967號公報
[專利文獻2]日本特公昭64-4508號公報
本發明係以提供安全性高且具有優良美白作用的美白劑作為課題。
本發明人等尋求具有美白作用的化合物而專心致力進行研究的結果，發現具有特定結構的胺基羧酸衍生物及其酸加成鹽發揮優良美白作用，得以完成本發明。
亦即，本發明之一態樣為含有下述通式(1)所表示之化合物或其酸加成鹽的美白劑。
(式中，X表示氫原子可被甲基取代之碳數1~2的伸烷基，Y表示COOR1或CH2OR2，R1表示氫原子或可具有分支之碳數1~6的烷基，R2表示氫原子或可具有分支之碳數1~6的醯基。)
又，本發明之另一態様為含有前述美白劑之美白用的皮膚外用組成物。前述皮膚外用組成物較佳為化妝品。
藉由本發明，而提供具有優良美白作用的美白劑。又，亦提供含有該美白劑之美白用的皮膚外用組成物，其適合作為化妝品。
本發明之美白劑含有下述通式(1)所表示之化合物或其酸加成鹽。
通式(1)中，X表示氫原子可被甲基取代之碳數1
~2的伸烷基。就碳數1~2的伸烷基而言，為亞甲基、及伸乙基。X較佳為-CH2-CH(CH3)-或-CH2-CH2-。
通式(1)中，Y表示COOR1或CH2OR2，R1表示氫原子或可具有分支之碳數1~6的烷基，R2表示氫原子或可具有分支之碳數1~6的醯基。
亦即，Y為COOR1之情形，R1為氫原子時Y為羧基，R1為可具有分支之碳數1~6的烷基時Y為酯基。就可具有分支之碳數1~6的烷基而言，可舉出例如：甲基、乙基、正丙基、異丙基、正丁基、異丁基、三級丁基、正戊基、正己基等。從美白作用的觀點來看，R1特佳為氫原子，又，R1為烷基時，其碳數更佳為較小者。
又，Y為CH2OR2之情形，R2為氫原子時Y為羥甲基，R2為可具有分支之碳數1~6的醯基時Y為酯基。就可具有分支之碳數1~6的醯基而言，可舉出例如：甲醯基、乙醯基、丙烯醯基、丙醯基、丙炔醯基、丁醯基、異丁醯基、甲基丙烯醯基、戊醯基、己醯基等。從美白作用的觀點來看，R2特佳為氫原子，又，R2為醯基時，其碳數更佳為較小者。
於通式(1)中，1,4-伸環己基可為椅型或船型之任一形態。又，2個鍵結鍵可為順式或反式之任一關係。較佳為椅型之形態且為反式之關係者。
就下述通式(1)所表示之化合物的酸加成鹽而言，可舉出與無機酸、有機羧酸、或有機磺酸之鹽。就無機酸而言，可舉出鹽酸、氫溴酸、硫酸、硝酸、磷酸等；就有機羧酸而言，可舉出乙酸、丙酸、馬來酸、富馬酸、草酸、檸檬酸、丁酸、乳酸、酒石酸等；就有機磺酸而言，可舉出甲磺酸、乙磺酸、苯磺
酸、對甲苯磺酸等。此等之中較佳為無機酸鹽，更佳為鹽酸鹽。
就本發明之美白劑的有效成分而言，可為通式(1)所表示之化合物或其酸加成鹽之任一者，但更佳為酸加成鹽者。
以下舉出通式(1)所表示之化合物的具體例，但當然並非僅被限定於此等。
2-[對-(4-胺基甲基環己基羰基)苯基]乙酸、2-[對-(4-胺基甲基環己基羰基)苯基]乙酸甲酯、2-[對-(4-胺基甲基環己基羰基)苯基]乙酸乙酯、2-[對-(4-胺基甲基環己基羰基)苯基]乙酸丙酯、2-[對-(4-胺基甲基環己基羰基)苯基]乙酸丁酯、2-[對-(4-胺基甲基環己基羰基)苯基]乙酸戊酯、2-[對-(4-胺基甲基環己基羰基)苯基]乙酸己酯；2-[對-(4-胺基甲基環己基羰基)苯基]乙醇、甲酸2-[對-(4-胺基甲基環己基羰基)苯基]乙酯、乙酸2-[對-(4-胺基甲基環己基羰基)苯基]乙酯、丙酸2-[對-(4-胺基甲基環己基羰基)苯基]乙酯、丁酸2-[對-(4-胺基甲基環己基羰基)苯基]乙酯、戊酸2-[對-(4-胺基甲基環己基羰基)苯基]乙酯、己酸2-[對-(4-胺基甲基環己基羰基)苯基]乙酯；2-[對-(4-胺基甲基環己基羰基)苯基]丙酸、2-[對-(4-胺基甲基環己基羰基)苯基]丙酸甲酯、2-[對-(4-胺基甲基環己基羰基)苯基]丙酸乙酯、2-[對-(4-胺基甲基環己基羰基)苯基]丙酸丙酯、2-[對-(4-胺基甲基環己基羰基)苯基]丙酸丁酯、2-[對-(4-胺基甲基環己基羰基)苯基]丙酸戊酯、2-[對-(4-胺基甲基環己基羰基)苯基]丙酸己酯；2-[對-(4-胺基甲基環己基羰基)苯基]丙醇、甲酸2-[對-(4-胺基甲基環己基羰基)苯基]丙酯、乙酸2-[對-(4-胺基甲基環己
基羰基)苯基]丙酯、丙酸2-[對-(4-胺基甲基環己基羰基)苯基]丙酯、丁酸2-[對-(4-胺基甲基環己基羰基)苯基]丙酯、戊酸2-[對-(4-胺基甲基環己基羰基)苯基]丙酯、己酸2-[對-(4-胺基甲基環己基羰基)苯基]丙酯；3-[對-(4-胺基甲基環己基羰基)苯基]丙酸(化合物1)、3-[對-(4-胺基甲基環己基羰基)苯基]丙酸甲酯、3-[對-(4-胺基甲基環己基羰基)苯基]丙酸乙酯、3-[對-(4-胺基甲基環己基羰基)苯基]丙酸丙酯、3-[對-(4-胺基甲基環己基羰基)苯基]丙酸丁酯、3-[對-(4-胺基甲基環己基羰基)苯基]丙酸戊酯、3-[對-(4-胺基甲基環己基羰基)苯基]丙酸己酯(化合物2)；3-[對-(4-胺基甲基環己基羰基)苯基]丙醇(化合物3)、甲酸3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、乙酸3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、丙酸3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、丁酸3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、戊酸3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、己酸3-[對-(4-胺基甲基環己基羰基)苯基]丙酯(化合物4)；2-甲基-3-[對-(4-胺基甲基環己基羰基)苯基]丙醇、甲酸2-甲基-3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、乙酸2-甲基-3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、丙酸2-甲基-3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、丁酸2-甲基-3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、戊酸2-甲基-3-[對-(4-胺基甲基環己基羰基)苯基]丙酯、己酸2-甲基-3-[對-(4-胺基甲基環己基羰基)苯基]丙酯(化合物5)。
通式(1)所表示之化合物可藉由常規方法來合成‧精製而取得。例如，可藉由專利文獻2所記載之胺基羧酸鹵化物之酸加成鹽在路易斯酸存在下的醯化反應來合成，且經過適當的
單離‧精製方法而製造。
通式(1)所表示之化合物及其酸加成鹽，因具有優良美白作用，而成為美白劑的有效成分。
此外，於本說明書中，美白係指色素沉著之預防及/或改善，更具體而言，係指斑點、暗沉、雀斑、曬黑、因皮膚的炎症或刺激所導致的變黑等之因黑色素產生亢進、過度蓄積、及沉著異常等而發生的色素沉著症狀、以及因類固醇等之藥物所導致的皮膚的黑變症等之因引起色素沉著之疾病等所導致的色素沉著症狀等之預防及/或改善。
關於本發明之美白劑的作用機制，詳細雖不明，但推測係藉由酪胺酸酶抑制作用、酪胺酸酶基因表現抑制作用、酪胺酸酶蛋白表現抑制作用、酪胺酸酶相關蛋白分解作用等之酪胺酸酶活性抑制作用、氫離子幫浦抑制作用、黑色素細胞之對角質細胞的黑素體輸送抑制作用、或新的作用機制，而預防及/或改善色素沉著。
本發明從另一層面來看，亦可謂包含應用通式(1)所表示之化合物或其酸加成鹽的美白方法或者色素沉著之預防及/或改善方法。
本發明從另一層面來看，亦可謂通式(1)所表示之化合物或其酸加成鹽用於美白或者用於色素沉著之預防及/或改善的用途。
本發明從另一層面來看，亦可謂通式(1)所表示之化合物或其酸加成鹽之在美白劑的製造中的用途。
本發明從另一層面來看，亦可謂為了美白或者色素沉著之預防及/或改善而使用之通式(1)所表示之化合物或其酸加成鹽。
通式(1)所表示之化合物的結構係與傳明酸部分地一致，但已知在活體內不會被代謝成傳明酸。亦即，通式(1)所表示之化合物的美白作用被認為係與傳明酸來自不同機制者，推測至少(4-胺基甲基環己基羰基)苯基之結構係參與該作用之發揮者。
此外，專利文獻1所記載的西查細特為傳明酸之酯衍生物，係藉由其自身的結構，及藉由酯鍵因代謝被切斷而成為傳明酸，來發揮美白作用。
本發明之美白劑可被含於美白用的組成物中，特佳為作成可期待來自經皮吸收的效果之皮膚外用組成物。就皮膚外用組成物之態樣而言，只要為藉由外用而被應用於皮膚者，則並不特別限定，但較佳可舉出化妝品(包含準醫藥品(Quasi-drug))、醫藥品等。通式(1)所表示之化合物已確認為高安全性，能夠以日常性使用之化妝品的態様來連續地塗布。
就皮膚外用組成物的劑型而言，並不特別限定，可舉出例如：洗劑(lotion)型、乳液或乳霜等之乳化劑型、油劑型、凝膠劑型、
泥敷劑、清潔劑等。
使美白用的皮膚外用組成物含有本發明之美白劑的情形，若將其量相對於組成物全量，以總量計設為較佳為0.01%~20質量%，更佳為0.1~10質量%，進一步較佳為1~5質量%之含量，則容易得到所期望的效果，還可確保處方設計的自由度。
本發明之美白用的皮膚外用組成物，除了本發明之美白劑以外，只要不損及本發明之效果，亦可任意地含有通常被摻合於皮膚外用組成物之成分。
就該成分而言，可舉出例如：澳洲胡桃油、鱷梨油、玉米油、橄欖油、菜籽油、芝麻油、蓖麻油、紅花子油、棉籽油、荷荷巴油、椰子油、棕櫚油、液體羊毛脂、硬化椰子油、硬化油、木蠟、硬化蓖麻油、蜂蠟、小燭樹蠟(candelilla wax)、巴西棕櫚蠟、蟲蠟(insects wax)、羊毛脂、還原羊毛脂、硬質羊毛脂、荷荷巴蠟(jojoba wax)等之油、蠟類；液體石蠟、鯊烷(squalane)、姥鮫烷(pristane)、地蠟(ozokerite)、石蠟、地蠟精(ceresin)、凡士林、微晶蠟等之烴類；油酸、異硬脂酸、月桂酸、肉荳蔻酸、棕櫚酸、硬脂酸、二十二酸(behenic acid)、十一烯酸等之高級脂肪酸類；鯨蠟醇、硬脂醇、異硬脂醇、二十二醇、辛基十二醇、肉荳蔻醇、鯨蠟硬脂醇等之高級醇等；異辛酸鯨蠟酯、肉荳蔻酸異丙酯、異硬脂酸己基癸酯、己二酸二異丙酯、癸二酸二-2-乙基己酯、乳酸鯨蠟酯、蘋果酸二異硬脂酯、乙二醇二-2-乙基己酸酯、新戊二醇二癸酸酯、二-2-庚基十一酸甘油、三-2-乙基己酸甘油、三羥甲基丙烷三-2-乙基己酸酯、三羥甲基丙烷三異硬脂酸酯、新戊四醇四-2-乙基己酸酯等之合成酯油類；二甲基聚矽氧烷、甲基
苯基聚矽氧烷、二苯基聚矽氧烷等之鏈狀聚矽氧烷；八甲基環四矽氧烷(octamethylcyclotetrasiloxane)、十甲基環五矽氧烷、十二甲基環六矽氧烷等之環狀聚矽氧烷；胺基改質聚矽氧烷、聚醚改質聚矽氧烷、烷基改質聚矽氧烷、氟改質聚矽氧烷等之改質聚矽氧烷等之矽油等之油劑類；脂肪酸皂(fatty acid soap)(月桂酸鈉、棕櫚酸鈉等)、月桂基硫酸鉀、烷基硫酸三乙醇胺醚等之陰離子界面活性劑類；氯化硬脂基三甲基銨、氯化苄烷銨(benzalkonium chloride)、氧化月桂基胺(laurylarmine oxide)等之陽離子界面活性劑類；咪唑啉系兩性界面活性劑(2-椰油基-2-氫氧化咪唑啉鎓物-1-羧乙氧基二鈉鹽(2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt)等)、甜菜鹼系界面活性劑(烷基甜菜鹼、醯胺甜菜鹼、磺基甜菜鹼等)、醯基甲基牛磺酸等之兩性界面活性劑類；山梨糖醇酐脂肪酸酯類(山梨糖醇酐單硬脂酸酯、山梨糖醇酐倍半油酸酯(sorbitan sesquioleate)等)、甘油脂肪酸類(單硬脂酸甘油等)、丙二醇脂肪酸酯類(丙二醇單硬脂酸酯等)、硬化蓖麻油衍生物、甘油烷基醚、POE山梨糖醇酐脂肪酸酯類(POE山梨糖醇酐單油酸酯、聚氧伸乙基山梨糖醇酐單硬脂酸酯等)、POE山梨糖醇脂肪酸酯類(POE-山梨糖醇單月桂酸酯等)、POE甘油脂肪酸酯類(POE-甘油單異硬脂酸酯等)、POE脂肪酸酯類(聚乙二醇單油酸酯、POE二硬脂酸酯等)、POE烷基醚類(POE2-辛基十二基醚等)、POE烷基苯基醚類(POE壬基苯基醚等)、Pluronic型類、POE‧POP烷基醚類(POE‧POP2-癸基十四基醚等)、Tetronic類、POE蓖麻油‧硬化蓖麻油衍生物(POE蓖麻油、POE硬化蓖麻油等)、蔗
糖脂肪酸酯、烷基葡萄糖苷等之非離子界面活性劑類；聚乙二醇、甘油、1,3-丁二醇、赤藻糖醇、山梨糖醇、木糖醇、麥芽糖醇、丙二醇、二丙二醇、二甘油、異戊二醇、1,2-戊二醇、2,4-己二醇、1,2-己二醇、1,2-辛二醇等之多元醇類；吡咯啶酮甲酸鈉(sodium pyrrolidone carboxylate)、乳酸、乳酸鈉等之保濕成分類；可經表面處理之雲母、滑石、高嶺土、合成雲母、碳酸鈣、碳酸鎂、無水矽酸(矽石)、氧化鋁、硫酸鋇等之粉體類；可經表面處理之紅丹、黃色氧化鐵、黑色氧化鐵、氧化鈷、群青、普魯士藍、氧化鈦、氧化鋅之無機顏料類；可經表面處理之雲母鈦、魚鱗箔(fish scale foil)、氧氯化鉍等之珠光劑(pearling agent)；可經色澱化之紅色202號、紅色228號、紅色226號、黃色4號、藍色404號、黃色5號、紅色505號、紅色230號、紅色223號、橙色201號、紅色213號、黃色204號、黃色203號、藍色1號、綠色201號、紫色201號、紅色204號等之有機色素類；聚乙烯粉末、聚甲基丙烯酸甲酯、耐綸粉末、有機聚矽氧烷彈性體等之有機粉體類；對胺苯甲酸系紫外線吸收劑；鄰胺苯甲酸系紫外線吸收劑；水楊酸系紫外線吸收劑；桂皮酸系紫外線吸收劑；二苯甲酮系紫外線吸收劑；糖系紫外線吸收劑；2-(2'-羥基-5'-三級辛基苯基)苯并三唑、4-甲氧基-4'-三級丁基二苯甲醯甲烷等之紫外線吸收劑類；乙醇、異丙醇等之低級醇類；維生素A或其衍生物、維生素B6鹽酸鹽、維生素B6三棕櫚酸酯、維生素B6二辛酸酯、維生素B2或其衍生物、維生素B12、維生素B15或其衍生物等之維生素B類；α-生育酚、β-生育酚、γ-生育酚、維生素E
乙酸酯等之維生素E類、維生素D類、維生素H、泛酸、泛雙硫醇、吡咯喹啉醌(Pyrroloquinoline quinone)等之維生素類等；對羥苯甲酸甲酯(methylparaben)、對羥苯甲酸乙酯(ethylparaben)、對羥苯甲酸丁酯(butylparaben)、苯氧乙醇等之抗菌劑(防腐劑)；甘草酸(glycyrrhizic acid)衍生物、甘草次酸(glycyrrhetinic acid)衍生物、水楊酸衍生物、扁柏酚(hinokitiol)、氧化鋅、尿囊素等之消炎劑；視黃醇、抗壞血酸、生育酚、或乙酸法呢酯(farnesyl acetate)等之皺紋改善劑；各種萃取物(例如，黃蘗樹皮(Phellodendron bark)、黃連、紫草根(Lithospermum root)、芍藥、當藥、白樺、鼠尾草、枇杷、胡蘿蔔、蘆薈、錦葵、鳶尾、葡萄、薏苡仁、絲瓜、百合、番红花、川芎、生薑、金絲桃、刺芒柄花(Ononis spinosa)、大蒜、辣椒、陳皮、當歸、海藻等)；蜂王漿、感光素、膽固醇衍生物等之活化劑；壬酸香草基醯胺(Nonanoic acid vanillylamide)、辣椒素、薑油酮、單寧酸等之血液循環促進劑；硫黃、二甲硫蔥(thianthol)等之抗脂漏劑(antiseborrheic drug)；傳明酸、硫代牛磺酸(thiotaurine)、亞牛磺酸(hypotaurine)等之抗發炎劑；膠原蛋白、玻尿酸等之水溶性高分子等。
又，將本發明之美白劑以外的美白劑一起摻合亦無妨。可舉出例如：烷基間苯二酚、抗壞血酸或其衍生物、胎盤萃取物、虎耳草或薏苡等之植物萃取物、熊果素等。
以下，舉出具體的實驗例進一步詳細說明本發明，但本發明並非僅被限定於以下之態様。
分別以常規方法調製表1所記載的化妝品(實施例1~9、比較例、及參考例)。
針對調製的各化妝品，藉由以下的方法評價美白效果(色素沉著的改善效果)。亦即，於自願參加之10位品評員(panelist)的左右上臂內側部設定合計8處之0.5cm×0.5cm的試驗部位。對所設定之部位以1日1次、連續3日而照射3次最小紅斑照射量(1MED)的紫外線照射。從試驗第1日的紫外線照射結束時(第1次照射結束後)起，以1日2次、連續25日而對比較例與剩餘的7處塗布各50μL的實施例1~9及參考例之任一化妝品。於25日的塗布結束24小時後，以色差計(CR-300，Konica Minolta股份有限公司)測定各試驗部位的皮膚亮度(L*值)，並自實施例或參考例之化妝品的塗布部位的L*值減去比較例之化妝品的塗布部位的L*值，藉此算出皮膚亮度之差(ΔL*值)。L*值由於色素沉著的程度越強則成為越低之值，因此可判斷ΔL*值越大，色素沉著越受到改善。
依據表3所示處方，調製為本發明之皮膚外用劑的化妝水。亦即，將A的成分以常溫、將B的成分以60℃分別加溫而混合，在攪拌下將B緩緩加入A，攪拌冷卻而得到化妝水。
已確認此化妝水在應用於皮膚時可得到美白效果。
依據表4所示處方，調製為本發明之皮膚外用劑的化妝水。亦即，將A的成分以常溫、將B的成分以60℃分別加溫而混合，在攪拌下將B緩緩加入A，攪拌冷卻而得到化妝水。
已確認此化妝水在應用於皮膚時可得到美白效果。
依據表5所示處方，調製為本發明之皮膚外用劑的精華液。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將B緩緩加入A，攪拌冷卻而得到精華液。
已確認此精華液在應用於皮膚時可得到美白效果。
依據表6所示處方，調製為本發明之皮膚外用劑的乳液。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將B緩緩加入A，攪拌冷卻而得到乳液。
已確認此乳液在應用於皮膚時可得到美白效果。
依據表7所示處方，調製為本發明之皮膚外用劑的O/W乳霜。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將B緩緩加入A，攪拌冷卻而得到O/W乳霜。
已確認此O/W乳霜在應用於皮膚時可得到美白效果。
依據表8所示處方，調製為本發明之皮膚外用劑的W/O乳霜。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將A緩緩加入B，攪拌冷卻而得到W/O乳霜。
已確認此W/O乳霜在應用於皮膚時可得到美白效果。
依據表9所示處方，調製為本發明之皮膚外用劑的O/W粉
底。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將B緩緩加入A，攪拌冷卻而得到O/W粉底。
已確認此O/W粉底在應用於皮膚時可得到美白效果。
依據表10所示處方，調製為本發明之皮膚外用劑的W/O粉底。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將A緩緩加入B，攪拌冷卻而得到W/O粉底。
已確認此W/O粉底在應用於皮膚時可得到美白效果。
依據表11所示處方，調製為本發明之皮膚外用劑的O/W防曬劑。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將B緩緩加入A，攪拌冷卻而得到O/W防曬劑。
已確認此O/W防曬劑在應用於皮膚時可得到美白效果。
依據表12所示處方，調製為本發明之皮膚外用劑的W/O防曬劑。亦即，將A及B的成分以80℃分別加溫而混合，在攪拌下將A緩緩加入B，攪拌冷卻而得到W/O防曬劑。
已確認此W/O防曬劑在應用於皮膚時可得到美白效果。
本發明之美白劑由於發揮優良美白效果，可適宜地被含於美白用的皮膚外用組成物中，於產業上非常有用。
Claims (3)
- 一種美白劑，其含有下述通式(1)所表示之化合物或其酸加成鹽，
- 一種美白用的皮膚外用組成物，其含有如請求項1之美白劑。
- 如請求項2之皮膚外用組成物，其係化妝品。
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| DE102006019044A1 (de) * | 2006-04-25 | 2007-10-31 | Merck Patent Gmbh | Antioxidantien |
| JP5133645B2 (ja) * | 2006-10-02 | 2013-01-30 | 第一三共ヘルスケア株式会社 | セトラキサートを含有する美白剤 |
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