TW201442736A - 局部美白組合物及其使用方法 - Google Patents
局部美白組合物及其使用方法 Download PDFInfo
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- TW201442736A TW201442736A TW103107515A TW103107515A TW201442736A TW 201442736 A TW201442736 A TW 201442736A TW 103107515 A TW103107515 A TW 103107515A TW 103107515 A TW103107515 A TW 103107515A TW 201442736 A TW201442736 A TW 201442736A
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- skin
- composition
- salt
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- thiodipropionic acid
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Abstract
本發明之實施例大體上係關於一種於化妝品上可接受之媒劑中包含美白劑、菸鹼醯胺及3,3'-硫二丙酸之組合物、其製品及使用方法。本文所述之該等組合物及方法能有效美白需要美白之皮膚區域,諸如(但不限於)具有整體皮膚黝黑、色素性皮膚變色、雀斑、老年斑、肝斑、太陽曬傷、曬黑、色素性痤瘡痕、疤痕、色素性胎記、色素過多、炎症後色素過多、損傷後色素過多、黑斑、黃褐斑、燒傷後疤痕、指甲染色、皮膚泛黃、黑眼圈及其類似症狀之個體。該組合物可再包括相應地用於彩色化妝品、保濕劑、潔面劑、化妝水及其類似物之其他成分。
Description
本發明大體上係關於化妝及皮膚用組合物及減少皮膚中之色素沉著之方法。本發明之組合物包含硫二丙酸或其衍生物與菸鹼醯胺或其衍生物組合。該等組合物可局部塗覆至皮膚以減少塗覆區域中之色素沉著。
若干皮膚病狀係與皮膚過度產生或不需要地產生黑色素相關,包括老年斑、雀斑及肝斑。黑色素之合成發生於皮膚中之黑色素細胞中且為涉及若干生物化學路徑之複雜過程。諸如氫醌及曲酸的一些皮膚美白劑或去色素劑充當酪胺酸酶(即一種在被稱為黑素體之細胞器內具有催化活性域之酶)之抑制劑。酪胺酸酶使包括酪胺酸之酚轉化為鄰醌,隨後在黑素體內轉化為黑色素。諸如絲胺酸-蛋白酶抑制劑的其他皮膚美白劑藉由破壞黑素體由黑素細胞至角質細胞(黑色素沈積於其中)之轉移而起作用。
儘管已發現諸如氫醌及曲酸之皮膚美白劑在化妝及皮膚用產品中之一些效用,但仍繼續需要有效減少皮膚色素沉著之產品。因此,本發明之目標為提供減少人類皮膚中之色素沉著,包括例如治療色素過多、不需要之色素沉著、老年斑、肝斑、雀斑及其類似症狀之組合物及方法。呈現出前面論述內容僅為了更好地理解此項技術所面臨之
問題的本質,且不應以任何方式理解為承認了先前技術,亦不應將本文中對任何參考文獻之引用理解為承認該參考文獻構成本申請案之「先前技術」。
根據前述及其他目標,本發明提供用於減少人類皮膚中之色素沉著之組合物及方法。該等組合物及方法可治療色素過多病狀,包括與UV損傷及時序衰老(chronological aging)相關之彼等病狀,包括(但不限於)治療、改善老年斑、肝斑、雀斑及其類似症狀、減少其出現或對其進行預防。該等組合物及方法亦適用於減少其他方面不需要之色素沉著,包括皮膚之整體美白。
在本發明之一態樣中,提供減少皮膚中之色素沉著之組合物,其包含有效量之用於抑制酪胺酸酶之3,3'-硫二丙酸(TDPA)或其酯或鹽與有效量之用於抑制黑素體轉移之菸鹼醯胺或其鹽或衍生物組合。該等組合物之特徵可在於有效量之硫二丙酸(TDPA)或其酯或鹽及菸鹼醯胺或其鹽或衍生物使黑色素減少,該黑色素減少比單獨藉由有效量之任一組分,亦即在不存在有效量之另一組分之情況下所實現之黑色素減少大至少25%,或大至少50%。在一些實施例中,組合物之特徵可在於有效量之硫二丙酸(TDPA)或其酯或鹽及菸鹼醯胺或其鹽或衍生物使黑色素合成至少大致累加性減少,意謂所得黑色素減少大致為藉由個別組分單獨實現之減少的總和。在其他實施例中,提供包含硫二丙酸(TDPA)及其酯以及菸鹼醯胺或其鹽或衍生物之組合的組合物,其使黑色素合成超過累加性減少,意謂所得黑色素減少超過藉由個別組分單獨實現之減少的總和。
在本發明之一些實施中,有效量之硫二丙酸(TDPA)或其酯或鹽可在以組合物之總重量計約0.001重量%至約10重量%、通常0.01重量%至約5重量%、或約0.1重量%至約2.5重量%、或約0.5重量%至約1.5
重量%之範圍內。在其他實施中,有效量之菸鹼醯胺或其衍生物可在以組合物之總重量計約0.0001重量%至約5重量%、通常0.001%至約5重量%或約0.01%至約2.5重量%之範圍內。有效量之硫二丙酸(TDPA)或其酯或鹽與有效量之菸鹼醯胺或其衍生物之重量比可在約100:1至約1:100範圍內,但通常將在約50:1至約1:50、更通常約25:1至約1:25或約15:1至約1:15;約10:1至約1:10;約5:1至約1:5;約3:1至約1:3;約2:1至約1:2;及約1:1之範圍內。在一個實施例中,硫二丙酸(TDPA)或其酯或鹽與有效量之菸鹼醯胺或其衍生物之重量比為約10:1。
本發明之組合物將通常包括化妝品上或皮膚學上可接受之媒劑,其可呈例如精華素、乳霜、洗劑、凝膠或棒膏形式,且可包含乳液(例如油包水、水包油、聚矽氧包水、水包聚矽氧、聚矽氧包多元醇、多元醇包聚矽氧乳液等),或可包含水性或乙醇媒劑、聚矽氧(例如環甲聚矽氧烷、二甲聚矽氧烷等)、烴(例如石蠟脂、異十二烷等)、酯油(十四烷酸異丙酯、十四烷酸十四烷基酯或其類似物。媒劑可進一步包含乳化劑、膠凝劑、規整劑、流變改質劑(例如增稠劑)、成膜劑或其類似物。本發明之組合物可視情況包括其他皮膚有益劑,諸如潤膚劑(二甲聚矽氧烷油、酯油或烴油)、保濕劑(例如多元醇,包括丙二醇、甘油等)、抗氧化劑(例如BHT、抗壞血酸、抗壞血酸鈉、棕櫚酸抗壞血酸酯、β-胡蘿蔔素等)、維生素(例如生育酚、生育酚乙酸酯等)、α-羥基酸(例如乙醇酸)、β-羥基酸(例如柳酸)、類視黃素(例如視黃酸、全反式視黃酸、視黃醛、視黃醇及視黃酯,諸如乙酸酯或棕櫚酸酯)、其他抗衰老成分(例如膠原蛋白刺激劑)以及其他去色素劑。
在本發明之另一實施例中,組合物可包括單獨或組合形式之任何以下成分:nilopala;patanga;chandana;ushira;manjshta;kumkuma;laksa;padmakesara;padmaka;yashtimadhu;ajakshira;ksheera;nyagrodhapada;及/或lodhra。
在本發明之另一實施例中,組合物可包括單獨或組合形式之任何以下成分:乙烯基二甲聚矽氧烷/甲基倍半氧矽烷交聯聚合物;聚矽氧交聯聚合物,諸如辛醯基甲聚矽氧烷(及)PEG-12二甲聚矽氧烷/PPG-20交聯聚合物;MQ/T丙基樹脂。
本發明之另一目標為提供包含向皮膚局部塗覆該等去色素組合物之方法。該組合物可每日一次或兩次或更頻繁地進行塗覆,且該治療方案可持續為獲得所需明顯色素沉著減少所需之時間長度,其可為例如一週、四週、八週或更長。可將組合物塗覆至人類角質表面(諸如皮膚)以治療、改善、減少或預防以下一或多者或延遲其開始:皮膚黝黑、色素性皮膚變色、色素性胎記、色素過多、炎症後色素過多、損傷後色素過多、雀斑、老年斑、肝斑、太陽曬傷、曬黑、色素性痤瘡痕、疤痕、黑斑、黃褐斑、燒傷後疤痕、指甲染色、皮膚泛黃或黑眼圈。
在閱讀以下本發明之實施方式,包括說明性實施例及實例之後,熟習此項技術者將瞭解本發明之此等及其他態樣。
本文揭示本發明之詳細實施例;然而,應理解所揭示之實施例僅說明可以各種形式實施之本發明。另外,結合本發明之各種實施例所給出之實例中之每一者意欲為說明性的而非限制性的。因此,本文中所揭示之特定結構及功能細節並不解釋為限制性的,但僅解釋為用於教示熟習此項技術者以各種方式使用本發明之代表性基礎。
本發明之前提為發現3,3'-硫二丙酸(TDPA)及菸鹼醯胺(3-吡啶甲醯胺)之組合使皮膚中之黑色素減少至令人驚奇之程度。此結果出人意料,因為TDPA在與其他酪胺酸酶抑制劑或黑素體轉移抑制劑組合
時提供之結果小於累加性結果。如在實例1中所表明,3,3'-硫二丙酸及菸鹼醯胺之組合提供之黑色素減少遠大於單獨任一藥劑,且至少達成黑色素之累相性減少。實例2表明TDPA與已知酪胺酸酶抑制劑曲酸之組合提供之效應實質上小於累相性效應,且實際上該組合並不比單獨曲酸更佳。類似地,實例3表明TDPA與黑素體轉移抑制劑之組合提供之效益同樣實質上小於累相性效益。因此,未預測出3,3'-硫二丙酸(TDPA)及菸鹼醯胺可產生黑色素之累相性減少。可藉由闡述於實例1-3中之方案測定藥劑或藥劑組合減少皮膚中之黑色素之能力。
本發明提供減少色素沉著及/或美白包括(但不限於)皮膚、毛髮、口唇及指甲之外皮系統之區域的組合物。在一實施例中,組合物為一旦塗覆至生物基質即使得該生物基質美白之局部組合物。如本文所用,「皮膚」係指包括皮膚、毛髮、口唇、指甲及其類似物之外皮系統之生物基質。
在一些實施例中,組合物及方法係用於治療色素過多,其包括相對於個體之基線色素沉著根除、減少、改善或逆轉由在皮膚及/或毛囊中生物合成且沈積於毛髮或皮膚中之不同類型黑色素中之一或多者之存在增加產生之個體色素沉著的程度。
在一些實施例中,組合物及方法係用於美白皮膚,其包括根除、減少、改善及/或逆轉個體色素沉著之基線程度。可藉由觀測個體之菲茨帕特里克(Fitzpatrick)量表值之變化來量測美白皮膚。菲茨帕特里克量表(亦稱為菲茨帕特里克皮膚分型測試或菲茨帕特里克原型量表)為用於皮膚顏色之數值分類模式,且仍為對皮膚顏色進行皮膚病學研究之辨識手段。菲茨帕特里克量表量測若干部分,包括基因配置、對曝露至太陽之反應及曬黑習慣,且將皮膚分類為六種類型:I型(得分0-7)係指白色、皮膚極白皙、雀斑、典型白化皮膚,其總是曬傷但從不會曬黑;II型(得分8-16)係指白色、皮膚白皙,其經常曬
傷或難以曬黑;III型(得分17-24)係指米色,其極為常見,且有時遭受輕度曬傷,逐漸曬黑成淺褐色;IV型(得分25-30)係指具有褐色色澤之米色皮膚,其為典型的地中海白種人皮膚,且很少曬傷,易於曬黑為中度褐色;V型(得分30以上)係指深褐色皮膚,其極少曬傷,極易曬黑;VI型係指黑色皮膚,其從不曬傷、極易曬黑且深度色素沉著。在本發明之一些實施例中,治療能夠使所治療之皮膚區域在菲茨帕特里克量表上改變至少一個或至少兩個皮膚類型。應理解,如本文所用,術語治療(treating/treatment)包括且包涵減小、改善、改良、緩解及/或消除衰老及/或環境壓力之皮膚影響,或以其他方式減少皮膚中之色素沉著出現。本發明組合物及方法適用於治療身體之大量區域中之皮膚的皮膚病,該等區域包括(但不限於)面部、前額、口唇、頸部、手臂、手部、腿部、膝部、腳部、胸部、背部、腹股溝、臀部、大腿及其類似區域。在一個實施例中,將組合物塗覆至面部、胸部及/或手部。
可實現的特定效益包括(但不限於)減少暗色或色素過多皮膚之色素沉著;減少老年斑或肝斑;減少色素性胎記、太陽曬傷、曬黑、色素性痤瘡痕、疤痕;使皮膚色調均勻或最佳;減少黑眼圈之出現;治療黑斑、黃褐斑、雀斑、燒傷後疤痕、皮膚泛黃及損傷後色素過多;美白頭皮、腿部、面部及其他需要增白及褪色之區域的毛髮;及移除或減少指甲染色。
本發明組合物及其使用方法不受美白劑之生理及/或化學效果之任何特定特徵限制。已知各種皮膚美白路徑且包括例如藉由降低黑素細胞中之酪胺酸酶活性以及抑制黑素體成熟以減少黑素生成而存在之彼等皮膚美白路徑。然而,咸信用於本發明組合物及方法中之美白劑藉由多種作用模式且藉由抑制黑色素由黑素細胞至角質細胞之轉移來進行美白。
本發明組合物之第一組分為包含3,3'-硫二丙酸、其鹽或具有式I結構之3,3'-硫二丙酸之酯的酪胺酸酶抑制劑:
其中R1及R2獨立地選自氫、基團L或基團Ra,其中Ra在每次出現時獨立地為脂族C1-20烴基;芳族C6-12烴基;C6-20烷基-芳基烴基;C6-20芳基-烷基烴基;或雜芳族基,前述中之每一者視情況經基團R或經1-6個選自氮、氧、硫或鹵素之雜原子取代;其中L為具有式-X1-(CR*2) n -X2-(CR*2) m -X3-之基團;其中X1、X2及X3在每次出現時獨立地為一鍵、-O-、-NRN-、-S-、-(OCH2CH2) p -、-(CH2CH2O) q -或基團R*,其中「p」及「q」獨立地為1至10之整數,且「n」及「m」獨立地為0至10之整數;R在每次出現時獨立地選自氫、-F;-Cl;-Br;-I;-OH;-OR*;-NH2;-NHR*;-N(R*)2;-N(R*)3 +;-N(R*)-OH;-N(→O)(R*)2;-O-N(R*)2;-N(R*)-O-R*;-N(R*)-N(R*)2;-C=N-R*;-N=C(R*)2;-C=N-N(R*)2;-C(=NR*)-N(R*)2;-SH;-SR*;-CN;-NC;-(C=O)-R*;-CHO;-CO2H;-CO2 -;-CO2R*;-(C=O)-S-R*;-O-(C=O)-H;-O-(C=O)-R*;-S-(C=O)-R*;-(C=O)-NH2;-(C=O)-N(R*)2;-(C=O)-NHNH2;-O-(C=O)-NHNH2;-(C=S)-NH2;-(C=S)-N(R*)2;-N(R*)-CHO;-N(R*)-(C=O)-R*;-(C=NR)-O-R*;-O-(C=NR*)-R*;-SCN;-NCS;-NSO;-SSR*;-N(R*)-C(=O)-N(R*)2;-N(R*)-C(=S)-N(R*)2;-SO2-R*;-O-S(=O)2-R*;-S(=O)2-OR*;-N(R*)-SO2-R*;-SO2-N(R*)2;-O-SO3 -;-O-S(=O)2-OR*;-O-S(=O)-OR*;-O-S(=O)-R*;-S(=O)-OR*;-S(=O)-R*;-NO;-NO2;-NO3;-O-NO;-O-NO2;-N3;-N2-R*;-N(C2H4);-Si(R*)3;-CF3;-O-CF3;-PR*2;-O-
P(=O)(OR*)2;-P(=O)(OR*)2;全氟烷基;脂族C1-C12烴基;C6-C12芳族烴基;C5-C12雜芳基;RN及R*係獨立地選自氫或飽和、部分飽和或芳族C1-C20烴基,視情況經基團R或經1-6個選自氮、氧、硫或鹵素之雜原子取代;其限制條件為R1及R2中之至少一者為基團L或R*;及其鹽。
在一個實施例中,式I結構之化合物為單酯。在另一實施例中,式I結構之化合物為二酯。在一個實施例中,R1及R2相同。在另一實施例中,R1及R2不同。在一個實施例中,式I結構之化合物為單或二酯,其中R1及/或R2各獨立地選自C1-20脂族烴基。在一個實施例中,式I結構之化合物為TDPA之二烷基酯。在另一實施例中,式I結構之化合物為TDPA之C6-16二烷基酯。在另一實施例中,TDPA之酯為3,3'-硫代二丙酸二月桂酯。
在一些實施例中,3,3'-硫代二丙酸酯或其單酯可以離子化或鹽形式存在。適合之鹽可由3,3'-硫代二丙酸酯或其單酯與諸如金屬(鈉)氫氧化物、氨或胺之鹼的反應形成。
本發明之組合物亦將包含具有式II結構之菸鹼醯胺或其衍生物:
其中「n」為整數0或1;使得當「n」為1時,化合物為N-氧化物,且當「n」為0時,不存在氧原子;Z係選自由以下組成之群:O、S、NH及NRN;其中Z通常為O;G及Q獨立地選自由以下組成之群:氫、RN、-COR、-CO2R、-C(=O)NHR、-C(=O)NR2、-PO3R、-S(O) m R、-NHR、-N=CHR、-NR(C=O)R;及-NRCO2R;其中「m」為0、1或2;且其中G及Q可一
起形成3-6員雜環;且其中Z及G可一起形成5或6員雜環;且在一個實施例中,G及/或Q為低碳烷基(甲基、乙基、丙基或丁基);X及Y獨立地選自基團R,且其中X及Y可一起形成4-6員環;且在一些實施例中,X及/或Y為氫;且其中R、RN及R*係如與式I結構相關之上文所定義;或其鹽。
本文所述之去色素劑各自之適用有效量為以組合物之總重量計約0.001重量%至約10重量%、或約0.005重量%至約5重量%、或約0.01重量%至約2.5重量%、或約0.05重量%至約1.5重量%、或約0.1重量%至約1重量%。在此等範圍內,本發明組合物中之去色素劑之適用量可佔所有組合物之約0.001重量%、約0.005重量%、約0.01重量%、約0.05重量%、約0.1重量%、約0.255重量%、約0.5重量%、約1重量%或約2重量%。可藉由將來自以上給定之範圍及個別數值之各去色素劑之範圍及/或適用量相加在一起而確定組合物中之兩種皮膚美白劑之總量。
在一個實施例中,菸鹼醯胺(或其鹽)及3,3'-硫二丙酸(或其鹽)各自為美白皮膚之有效量,該量將通常在以組合物之總重量計約0.001%至約5%之範圍內。菸鹼醯胺或其鹽之有效量可為在例如以組合物之總重量計約0.01%至約0.5%(w/w)或約0.05%至約0.25%(w/w)之範圍內、約0.1%。3,3'-硫二丙酸或其鹽之有效量可為例如以組合物之總重量計約0.1%至約2.5%(w/w)或約0.5%至約1.5%(w/w)或約1%(w/w)之有效量。
組合物可包括化妝品上或皮膚學上可接受之媒劑。該等媒劑可呈任何此項技術中已知適合於塗覆至皮膚之形式。媒劑可佔組合物之約50重量%至約99重量%。
媒劑可包含水相、油相、醇、聚矽氧相或其混合物,且可呈乳液形式。合適乳液的非限制性實例包括油包水乳液、水包油乳液、水
包聚矽氧乳液、聚矽氧包水乳液、聚矽氧包多元醇乳液、多元醇包聚矽氧乳液、油包多元醇乳液、多元醇包油乳液、水包蠟乳液、水-油-水三重乳液或其類似物。乳液可包括乳化劑,諸如非離子型、陰離子型或兩性界面活性劑;或膠凝劑。
媒劑可包含水;植物油;礦物油;酯,諸如棕櫚酸辛酯、十四烷酸十四烷基酯、十四烷酸異丙酯及棕櫚酸異丙酯;醚,諸如二辛基醚及異山梨醇二甲醚;醇,諸如乙醇及異丙醇;脂肪醇,諸如鯨蠟基醇、鯨蠟硬脂醇及硬脂醇;揮發性聚矽氧,諸如環甲聚矽氧烷,聚矽氧油,如二甲聚矽氧烷、胺基封端二甲聚矽氧烷及二甲聚矽氧烷醇;烴,諸如礦物油、石蠟脂及異烷烴,諸如異辛烷、異十二烷(IDD)、異十六烷及異二十烷;及(氫化)聚烯烴,諸如聚異丁烯;多元醇,諸如丙二醇、甘油、丁二醇、戊二醇及己二醇;脂質體;蠟(動物、植物或合成蠟);或前述之任何組合或混合物。
在本發明之一個實施例中,組合物可包括其他皮膚活性劑,包括(但不限於)類視黃素、植物性治療藥物、角質溶解劑、脫皮劑、角質細胞增殖增強劑、膠原蛋白酶抑制劑、彈性蛋白酶抑制劑、去色素劑、消炎劑、類固醇、抗痤瘡劑、抗氧化劑及晚期糖基化終點產物(AGE)抑制劑。此等各種成分之量為化妝品領域中習用於達成其預期目的時之量,且通常在以組合物之重量計約0.01重量%至約20重量%之範圍內。此等成分之性質及其量必須與本發明之組合物的製法相容。在本發明之另一實施例中,組合物可包括單獨或組合形式之任何以下成分:nilopala;patanga;chandana;ushira;manjshta;kumkuma;laksa;padmakesara;padmaka;yashtimadhu;ajakshira;ksheera;nyagrodhapada;及/或lodhra。
組合物可包含具有抗衰老效應之其他活性成份,因為可能由該等組合獲得協同性改良。抗衰老組分實例包括(但不限於)植物性治療
藥物(例如紫鉚(Butea frondosa)萃取物);植醇;類視黃素(例如9-順式視黃酸、13-順式視黃酸、全反式視黃酸及其衍生物,植烷酸,視黃醇(維生素A)及其酯,諸如視黃醇棕櫚酸酯、視黃醇乙酸酯及視黃醇丙酸酯及其鹽及其他者);羥基酸(包括α-羥基酸及β-羥基酸)、柳酸及柳酸烷基酯;去角質劑(例如乙醇酸、3,6,9-三氧雜十一烷二酸等),雌激素合成酶刺激化合物(例如咖啡鹼及衍生物);能夠抑制5α-還原酶活性之化合物(例如次亞麻油酸、亞麻油酸、非那雄安(finasteride)及其混合物);及障壁功能增強劑(例如腦醯胺、甘油酯、膽固醇及其酯、α-羥基及ω-羥基脂肪酸及其酯等)(僅列舉數例)。
例示性類視黃素包括(但不限於)視黃酸(例如全反式或13-順式)及其衍生物、視黃醛、視黃醇(維生素A)及其酯(諸如視黃醇棕櫚酸酯、視黃醇乙酸酯及視黃醇丙酸酯)及其鹽。可特別提及視黃醇。當存在時,類視黃素之包括量通常將為約0.0001重量%至約5重量%、更通常約0.01重量%至約2.5重量%或約0.1重量%至約1.0重量%。此實施例之組合物通常將包括抗氧化劑,諸如抗壞血酸及/或BHT,及/或螯合劑,諸如EDTA或其鹽。
在另一實施例中,本發明之局部組合物亦可包括以下中之一或多者:皮膚穿透增強劑;潤膚劑,諸如十四烷酸異丙酯、石蠟脂、揮發性或非揮發性聚矽氧油(例如甲聚矽氧烷、二甲聚矽氧烷)、酯油、礦物油及脂肪酸酯;保濕劑,諸如甘油、己二醇或辛醯基乙二醇;皮膚豐潤劑,諸如軟脂醯基寡肽、膠原蛋白、膠原蛋白及/或葡糖胺聚糖(GAG)增強劑;防曬劑,諸如埃文苯酮(avobenzone);去角質劑;及抗氧化劑。
適合之去角質劑包括例如α-羥基酸、β-羥基酸、氧雜酸、氧雜二酸及其衍生物,諸如其酯、酸酐及鹽。適合之羥基酸包括例如乙醇酸、乳酸、蘋果酸、酒石酸、檸檬酸、2-羥烷酸、杏仁酸、柳酸及其
衍生物。一種例示性去角質劑為乙醇酸。當存在時,去角質劑可佔組合物之約0.001重量%至約20重量%。
可用於本發明組合物中之抗氧化劑之實例包括具有酚羥基官能基之化合物,諸如抗壞血酸及其衍生物/酯;β-胡蘿蔔素;兒茶素;薑黃素;阿魏酸衍生物(例如阿魏酸乙酯、阿魏酸鈉);五倍子酸衍生物(例如五倍子酸丙酯);番茄紅素;還原酸;迷迭香酸;鞣酸;四氫薑黃素;生育酚及其衍生物,包括生育酚乙酸酯;尿酸;或其任何混合物。其他適合之抗氧化劑為具有一或多個硫醇官能基(-SH)且呈已還原或未還原形式之彼等抗氧化劑,諸如麩胱甘肽、硫辛酸、硫代乙醇酸及其他硫氫基化合物。抗氧化劑可為無機物,諸如亞硫酸氫鹽、偏亞硫酸氫鹽、亞硫酸鹽或含有硫之其他無機鹽及酸。抗氧化劑可佔組合物之總重量之約0.001%至約10%(w/w)或約0.01%至約5%(w/w)。
組合物可包括一或多種對抗色素沉著或色素過多之其他藥劑,包括酪胺酸酶抑制劑及/或黑素體轉移抑制劑。可特別提及氫醌及其單苯甲基醚;氫醌-β-D-葡萄哌喃糖苷;類視黃素(例如視黃酸);維甲酸;壬二酸;曲酸(5-羥基-4-哌喃-4-酮-2-甲基);對甲氧酚(4-羥基苯甲醚);大豆蛋白及其他絲胺酸蛋白酶抑制劑;楮樹萃取物;甘草黃酮(甘草萃取物);地被熊果(Arctostaphylos patula)及白葉熊果(Arctostaphylos viscida)萃取物;光果甘草(Glycyrrhiza glabra)及其衍生物;小球藻(Chlorella vulgaris)萃取物;L-抗壞血酸基-2-磷酸鎂(MAP);4-異丙基兒茶酚;蘆薈素;N-乙醯基-4-S-半胱胺基酚及N-丙醯基-4-S-半胱胺基酚;N-乙醯基葡糖胺;及胺甲環酸(反-4-胺基甲基環己烷甲酸);熊果苷、熊葡萄萃取物、抗壞血酸及/或其衍生物、紫蘇萃取物(例如在美國專利第5,980,904號及日本公開案第07025742、07187989、10265322、2001163759及2001181173號中,該等文獻以引用之方式併入本文中)、椰果萃取物(日本專利第2896815B2號,該文
獻以引用之方式併入本文中)、椰子汁及鈣流入抑制劑(僅列舉數例)。一些實施例中可包括揭示於KR 2005095167;JP 2003252743;及JP 61260009(該等文獻以引用之方式併入本文中)中之酪胺酸抑制劑中之任一者。
其他皮膚美白劑包括以下之萃取物:紫鉚、補血草(Naringi crenulata)、烏蕨(Stenoloma chusana)、印楝(Azadirachta indica)、洋甘草(Glycyrrhiza glabra linn.)、海巴戟(Morinda citrifolia)、番茄糖脂、抗壞血酸基葡糖苷、維生素C、視黃醇及/或其衍生物、皺葉酸模萃取物、包括水解牛奶蛋白之牛奶蛋白、N,N,S-參(羧甲基)半胱胺、齊墩果酸、胎盤萃取物、虎耳草(saxifragia sarmentosa)、檜酸、川芎(ligusticum chiangxiong hort.)、紫萁(asmunda japonica thunb.)、繁縷(stellaria medica(L.)cyr.)、垂盆草(sedum sarmentosum bunge)、槁本(ligusticum lucidum Ait.)、冬青(ilex purpurea hassk)、油柑子、芹黃素、抗壞血酸基棕櫚醇、carruba C.borealis s、橙皮素、inabata C.borealis、異甘草素、堪非醇-7-新橙皮糖、L-含羞草鹼、葉黃酮、油可溶甘草萃取物P-T(40)、氧雜酸、異硫氰酸苯酯、可可素(cococin)、水飛薊素、T4CA、四氫薑黃素、尤尼諾(unitrienol)、熊果酸-齊墩果醇酸、UVA/URSI、或其任何組合。
任何該等其他去色素劑(即使存在)將通常以組合物之重量計約0.001重量%與約20重量%之間、或0.1重量%至10重量%之量存在。在本發明之一些實施例中,組合物不包含其他去色素劑或將基本上不含其他去色素劑,其意謂任何其他酪胺酸酶抑制劑及/或黑素體轉移抑制劑(即使存在)將以對於皮膚著色不具有可量測或臨床上可觀測之影響之低量存在。
其他添加劑包括:維生素,諸如生育酚及抗壞血酸;維生素衍生物,諸如單棕櫚酸抗壞血酸酯、生育酚乙酸酯及維生素E棕櫚酸
酯;增稠劑,諸如羥烷基纖維素、羧甲基纖維素、卡波姆(carbomber)及植物膠(諸如三仙膠);膠凝劑,諸如酯封端聚酯醯胺;規整劑;金屬螯合劑,諸如EDTA或其鹽;顏料;著色劑;及pH調節劑(檸檬酸、乙醇胺、氫氧化鈉等)。組合物可視情況包含熟習此項技術者已知之其他組分,包括(但不限於)成膜劑、增濕劑、礦物質、黏度及/或流變改質劑、抗痤瘡劑、防蟲劑、皮膚冷卻化合物、護膚劑、潤滑劑、芳香劑、防腐劑、穩定劑及其混合物。除前述者外,本發明之化妝用組合物可含有用於治療皮膚病症的任何其他化合物。
另外,本發明所涵蓋之組合物可包括一或多種相容的化妝品上可接受之佐劑,其為熟練醫師常用且已知的,諸如著色劑、珍珠、褐色珠光劑(chromalite)、雲母、顏料、染料、芳香劑、潤膚劑、保濕劑、防腐劑、維生素、螯合劑、增稠劑、麻醉劑、抗過敏劑、抗真菌劑、抗微生物劑、其他消炎劑、抗氧化劑、抗菌劑、去色素劑、成膜劑、防蟲劑、醫藥劑、光穩定劑、防曬劑、穩定劑、界面活性劑、增稠劑、黏度改質劑及植物性治療藥物。本發明之局部組合物亦可包括皮膚穿透增強劑、表面光滑劑、皮膚豐潤劑、光學漫射劑、剝離促進劑及抗氧化劑。關於此等及其他適合之化妝用成分的細節可見於由美國化妝品、盥洗用品和香水協會(Cosmetic,Toiletry,and Fragrance Association,CTFA)出版之「International Cosmetic Ingredient Dictionary and Handbook」第10版(2004),第2177-2299頁,該文獻以全文引用之方式併入本文中。此等各種物質之量為習知地用於化妝用或醫藥領域中之彼等量,例如,其可構成組合物總重量之約0.01%至約20%。
可包括防曬劑以保護皮膚免受有害紫外線之害。在本發明之一說明性實施例中,防曬劑藉由使用單一防曬劑或防曬劑之組合來提供UVA及UVB保護。可用於本發明組合物之防曬劑中有埃文苯酮、肉桂
酸衍生物(諸如肉桂酸辛基甲氧基酯)、柳酸辛酯、氧苯酮、奧克立林(octocrylene)、二氧化鈦、氧化鋅或其任何混合物。防曬劑可以組合物總重量之約1重量%至約30重量%存在。
組合物可調配為尤其用於局部投與之各種產物形式,諸如乳液、洗劑、乳霜、精華素、噴霧、氣溶膠、餅狀物、軟膏、精華液、凝膠、糊劑、貼片、筆狀物、濕巾、遮罩、棒膏、發泡體、酏劑、濃縮物及其類似物。組合物通常經調配呈乳液、洗劑、乳霜、軟膏、精華素或凝膠形式。組合物可調配至脂質體中,該等脂質體可包含其他添加劑或物質,及/或可經改質以在投與之後更特定到達或保持於一定部位。
在一個實施例中,局部組合物將具有1至8之pH範圍,其中2至7範圍內之pH為典型的。在一些實施例中,組合物將具有3.5至5.5範圍內之pH。可添加適合之pH調節劑(諸如檸檬酸及三乙醇胺)以使pH在所需範圍內。
本發明之另一實施例係關於藉由使用靶向傳遞系統(例如脂質體、微球粒(參見例如Unger等人之美國專利第5,770,222號)及其類似物)傳遞所述組合物,使得組分及/或活性成分可更容易到達且影響塗覆區域(例如面部或頸部或皮膚之其他區域)的皮下層。
在某些實施例中,本文所述之化妝用組合物可用於治療及/或預防皮膚之色素過多及/或毛髮之色素過多,例如用於美白皮膚或毛髮。在一些實施例中,將包含有效量之TDPA/菸鹼醯胺組合之組合物局部塗覆至皮膚或毛髮,例如塗覆至色素過多之皮膚或毛髮之區域。色素過多包括比個體所需更深且係由黑素細胞造成的個體之皮膚或毛髮之任何著色。該不需要之色素沉著亦可稱為變色。皮膚之色素過多區域包括離散或斑點狀色素過多。離散色素過多區域可為分離且均一之較深顏色區域,且可呈現為皮膚上之褐色斑點或雀斑,包括通常稱
為色素斑或「老年斑」之標記。皮膚之斑點狀色素過多區域可為深色斑塊,該等斑塊在尺寸及形狀上比離散色素沉著區域更大且更不規則。色素過多區域亦包括褐色皮膚區域,例如由於曝露於UV而引起之褐色皮膚。色素過多毛髮包括比所需更深之任何色度的毛髮。
皮膚色素過多可由任何因素造成,包括例如遺傳;曝露於UV或太陽;年齡;疤痕或由於皮膚損傷(包括撕裂、燒傷、曬傷、痤瘡或其他皮膚病)引起的變色及其類似因素。舉例而言,皮膚色素過多區域包括黑斑塊。黑斑為涉及面部皮膚變色之常見皮膚病症,面部皮膚變色為懷孕女性中普遍之一個實施例,此時其稱為面部黃褐斑或黃褐斑。黑斑(或黃褐斑)塊可在面部、面頰上部、鼻部、口唇、上唇及前額呈現為深褐色不規則斑塊。斑塊通常隨時間逐漸發展,且一般而言不發癢或發生其他方面的傷害,但可能對個體之外觀有負面影響。皮膚色素過多亦指例如已變為或正變得比所需更深的手臂下方區域。
皮膚色素過多可或可不包括比個體所需更深、通常被稱作「黑眼圈(under eye dark circle或dark circle)」之個體眼部下方之區域。黑眼圈通常為每隻眼睛下方之圓形、均一之色素沉著區域,其可由遺傳、過敏、疲勞或其他原因造成。在一個實施例中,局部塗覆組合物以治療黑眼圈。然而,在一些實施例中,治療色素過多不包括治療眼部下方面部皮膚之變色及/或鬆弛下垂,因為該色素沉著可能伴有與其他色素過多病狀無關之病因。色素過多皮膚亦可包括腋下(亦即手臂下方)區域中之皮膚。
治療色素過多或色素過多皮膚/毛髮係指根除、減少、改善或逆轉一或多種與色素過多相關之不需要之特徵,諸如在受影響之區域中產生可察覺的皮膚或毛髮之美白。在一個實施例中,可能需要美白皮膚之色素過多區域以消除老年斑;美白日光色素沉著;使皮膚色調均勻或最佳,例如在斑點狀色素過多區域中;治療黑斑塊或黃褐斑塊、
雀斑、燒傷後疤痕及損傷後之色素過多。預防色素過多或色素過多皮膚係指向未受色素過多影響之皮膚提供用以避免、延遲、防止或最小化一或多種與皮膚色素過多相關之不需要之特徵(諸如減小最終發展之色素過多區域的暗度或尺寸)的益處。
本發明組合物能夠治療及/或預防色素過多皮膚且可被稱作「皮膚美白劑」。當用於美白毛髮時,其可稱為「毛髮美白劑」。在一個實施例中,本發明之組合物可用於以非漂白方式美白毛髮;亦即藉由抑制黑色素自毛囊黑素細胞中形成及/或輸送,而非藉由漂白毛髮本身實現。在一個實施例中,藉由本發明美白之毛髮包括面部毛髮(例如上唇以上之毛髮)及體毛(例如手臂及腿部),其與頭髮相對。在一個實施例中,將該毛髮美白劑塗覆至位於上唇上之面部毛髮。
將組合物塗覆至皮膚持續足以減少皮膚中之黑色素出現之時間期。可每日局部塗覆組合物一次、兩次或兩次以上。可持續治療一週、兩週、四週、八週或八週以上之時間期。在一個實施例中,本發明之組合物將依約0.001至約100mg/cm2、更通常約0.01至約20mg/cm2或約0.1至約10mg/cm2之量塗覆至皮膚。
詳言之,包含菸鹼醯胺之美白劑或諸如抗壞血酸菸鹼醯胺之前體;二甲基聚矽氧烷之聚矽氧化合物;4-第三丁基-4'-甲氧基二苯甲醯基甲烷、甲氧基肉桂酸-2-乙基己基酯或其混合物之防曬劑;及媒劑之美白組合物並不計畫作為本文所述美白組合物之一。
本發明組合物提供產品,尤其為有需要之皮膚美白之皮膚護理及化妝用產品。有需要之皮膚包括(但不限於)皮膚黝黑、色素過多皮膚、老年斑、肝斑、變色或不均勻皮膚、黑眼圈,例如具有黑斑、黃褐斑、雀斑、燒傷後疤痕之皮膚、損傷後色素過多皮膚、需要增白或褪色之皮膚、頭皮、腿部、面部及其他區域、泛黃之皮膚、染色之指甲及其類似物。此外,本發明組合物可經調配以傳遞一致含量之活性
成分或成分摻合物,以便達到所需美容效果。
本發明之一個實施例係關於塗覆有效量之本文所述之美白組合物,以美白如本文所採用皮膚之受影響區域之方法。在一個實施例中,美白組合物為每日局部塗覆一次或兩次,其中需要美白之皮膚之受影響區域包括(但不限於)面部、頸部、手部、手臂、腿部、腳部、大腿、毛髮、頭皮及全身。美白組合物可視用途而定,保持於需要美白之受影響區域上或可沖洗掉或以其他方式移除。為維持所需美白效果,該方案應持續美白效果所需之時間長度。一旦中斷塗覆美白組合物,則所需美白效果亦將減小。
在一相關實施例中,將本發明組合物塗覆至人類皮膚,以減少皮脂產生或改良受脂肪團影響之皮膚外觀及/或減少不需要之脂肪生成或增加脂肪分解。在此實施例中,組合物可於化妝品上可接受之媒劑(如本文所描述)中進行調配,且在面部組合物之情況下可包括一或多種其他藥劑,諸如抗痤瘡成分(例如柳酸、過氧化苯甲醯及其他過氧化物、硫、類視黃素等),或在脂肪團治療之情況下,調配物可包含適合於治療脂肪團之任何成分,包括(但不限於)紫蘇油及其他不飽和脂肪油及ω-3脂肪酸,諸如α-次亞麻油酸;咖啡鹼;茶鹼;黃嘌呤;類視黃素(例如視黃醇);及其類似物。本發明之脂肪團治療通常將局部施加至受脂肪團之苦的皮膚(包括臀部及大腿之皮膚)上,持續足以改良其外觀之時間期,包括例如持續至少四週、至少八週、至少十二週或更久之每日治療。
在一些實施例中,式I(a)或I(b)之化合物將用於治療時序及環境衰老之病徵,包括減小細紋或皺紋之嚴重強度、治療皮膚稀薄(其包括使已變薄的皮膚增厚)及治療皮膚下垂。在此實施例中,化合物通常與視黃醇組合。通常將組合物每日一次、兩次或三次塗覆至皮膚持續實現所需結果所必需之時間長度。治療方案可包含每日塗覆持續至
少一週、至少兩週、至少四週、至少八週或至少十二週或十二週以上。亦涵蓋長期治療方案。組合物對細紋及皺紋形成或出現之影響可例如藉由目視檢驗以定性方式評估,或例如藉由對皺紋形態之顯微鏡或電腦輔助量測(例如每單位面積皮膚中皺紋之數目、深度、長度、面積、體積及/或寬度)以定量方式評估。
在其他實施例中,將組合物局部塗覆至皮膚以實現皮膚之美觀性改良。人類皮膚之美觀性改良可為皮膚之任何屬性或特徵之改良,包括(但不限於):(a)治療、減少及/或預防細紋或皺紋;(b)減小毛孔尺寸;(c)改良皮膚厚度、豐潤度及/或緊度;(d)改良皮膚光滑度、柔韌度及/或柔軟度;(e)改良皮膚色調、光亮度及/或透明度;(f)改良原膠原及/或膠原蛋白產生;(g)改良彈性蛋白之維護及重塑;(h)改良皮膚紋理及/或促進再組織化;(i)改良皮膚障壁修復及/或功能;(j)改良皮膚輪廓外觀;(k)恢復皮膚光澤及/或亮度;(l)補充皮膚中之必需養分及/或成分;(m)改良因衰老及/或閉經而降低之皮膚外觀;(n)改良皮膚保濕;(o)增加皮膚彈性及/或回彈性;(p)治療、減少及/或預防皮膚下垂;(q)改良皮膚堅實度;(r)減少色素斑及/或斑點狀皮膚;
(s)改良因光繞射或反射造成之皮膚光學特性;及(t)改良皮膚美白性。
在一個實施例中,組合物意欲用作非治療性治療。在另一實施例中,組合物為根據美國FD&C法案,§201(i)意欲擦、倒、撒或噴至人體上、引入人體中或以其他方式塗覆至人體以用於清潔、美化、促進吸引性或改變外觀之物品。
以下實例說明本發明說明書之特定態樣。不應將實例理解為限制性的,因為實例僅提供實施例及其各種態樣之特定理解及實踐。
使用MELANODERMTM(MEL-300-B,MatTek Corp.,Ashland,MA)人體皮膚模型研究3,3'-硫二丙酸或硫二丙酸(TDPA)及菸鹼醯胺對黑色素含量之影響。MELANODERMTM為含有來源於非洲-美國供體之黑素細胞之活復原三維人體皮膚等效物。如製造商所推薦,將組織在37℃下維持於培養基EPI-100-NMM-113中。
將TDPA溶解於水中達1.0%(w/v)之最終濃度。將菸鹼醯胺溶解於培養基中達0.1%(w/v)之最終濃度。將25μl TDPA溶液局部塗覆至MELANODERMTM組織,同時在第1、2、4、7、9及11日添加含有0.1%菸鹼醯胺之培養基。僅用水媒劑處理對照組織。用「飽和濃度」之兩種活性美白劑處理組織,該飽和濃度為對系統無毒之最高處理濃度。
在第14日,收集組織且在含有1% SDS、50mM EDTA及10mM Tris(pH 6.8)之緩衝液中均質化。向各勻漿中添加蛋白酶K(5mg/ml)且在45℃下培育隔夜。再添加蛋白酶K且在45℃下培育4小時,接著添加0.5M碳酸鈉及30% H2O2且在80℃下培育30分鐘。使樣品冷卻至
室溫,且用氯仿/甲醇(2:1)萃取。以10,000g離心10分鐘之後,量測450nm下頂部相之吸收率。相對於對照物計算經處理組織中黑色素含量之百分比變化。三種組織之黑色素含量之平均值顯示於表1中。單獨TDPA及菸鹼醯胺處理顯示相對於對照物黑色素顯著減少。但當二者組合時,其顯示在統計學上顯著大於單獨各者之黑色素之進一步減少。TDPA及菸鹼醯胺之共處理使黑色素含量減少26.3%,表明黑色素減少之量值為個別處理之組織之累加。
表1顯示在飽和濃度下之TDPA及菸鹼醯胺之共處理提供美白之完全100%累加效果。組合之黑色素減少比單獨使用菸鹼醯胺多出約60%且比單獨使用TDPA多出約160%。
*相對於媒劑對照物,p<0.05,**相對於單獨TDPA或菸鹼醯胺,p<0.05
藉由使用B16黑素瘤細胞進行檢定來測定3,3'-硫二丙酸及曲酸對黑色素含量之影響。已知此等細胞組成性地製造黑色素且為用於監測黑色素合成之抑制的常用且已接受之模型系統。
將B16小鼠黑素瘤細胞接種(ATCC,目錄號:CRL-6475)至96孔組織培養物處理盤(BD Falcon)中且於無酚紅之DMEM(Mediatech;目錄號:17-205-CV)中用測試活性劑或對照物處理。檢測細胞調節色素
形成之能力。使細胞曝露至稀釋之測試活性劑或對照物經7天之時間期,其中曲酸之最終濃度為0.01%,TDPA之最終濃度為0.1%,且使用每200微升最終體積2微升之水媒劑對照物。各自以6個複製品進行測試。在處理時間期之後,藉由使用標準微定量盤式讀取器(Tecan Group Ltd.)讀取540nm下之吸收率來定量產生之色素或合成之黑色素之含量。
在定量黑色素之量之後,使用MTT轉化法測定細胞活力。MTT轉化法藉由NAD(P)H依賴性微粒體去氫酶(其僅在活細胞中起作用)量測自黃色水溶性四唑鎓鹽之MTT染料還原為藍紫色不溶甲沈澱。藍色之強度指示細胞活力。在定量所產生之黑色素之量之後,使細胞曝露至MTT染料溶液(1mg/ml)兩至三小時。藉由試劑醇(95%乙醇:5%異丙醇)溶解甲材料且在迴轉式震盪器上震盪15-30分鐘。藉由使用微定量盤式讀取器在570nm下量測萃取之甲來測定活細胞之MTT染料吸收及轉化。計算總色素沉著、校正為細胞活力值且表示為相對於所進行之六個複製品之對照物之黑色素含量之平均百分比變化。
表2顯示使用B16黑素瘤細胞檢定得到之藉由曲酸(一種已知增白劑)及TDPA之共處理對黑色素含量之影響。儘管曲酸(增白之陽性對照物)及TDPA個別處理之細胞顯示色素沉著之百分比變化有一些減少,但在單獨曲酸與曲酸及TDPA之共處理之間不存在顯著差異。若組合具有累加效果,則預期百分比減少將為75%而非46.9%。此表明簡單任何去色素劑之組合未必會產生累加去色素效果。
*相對於媒劑對照物,p<0.05,#相對於TDPA但不相對於曲酸,p<0.05
根據描述於實例1中之方法使用MELANODERMTM人類皮膚模型研究TDPA及大豆胰蛋白酶抑制劑(STI)對黑色素含量之影響。
此實例提供用於具有額外抗衰老益處之皮膚美白化妝品之例示性調配物。所有成分量係指示為總體例示性化妝用組合物之(w/w)百分比。
此實例提供具有皮膚美白益處之除臭劑之例示性調配物。所有成分量係指示為總體例示性化妝用組合物之(w/w)百分比。
可藉由多達20重量%之量的三氯羥鋁鋯替換氫氯酸鋁。組合物呈固體棒膏形式且每日塗覆至手臂下方以減少腋下色素沉著。
為更充分地描述本發明所屬技術之當前水平,如本文所引用之所有專利、專利申請案、公開文章、摘要、書籍、參考手冊及文摘之內容均以全文引用之方式併入本文中。
因為可在不背離本發明之範疇及精神之情況下對上述標的物作出各種改變,所以在上述描述中所包含或所附申請專利範圍中所界定之所有標的物均意欲理解為本發明之描述性及說明性標的物。根據上述教示可對本發明作出許多修改及改變。因此,本說明書意欲涵蓋屬於隨附申請專利範圍之範疇的所有該等替代方案、修改及變化。
Claims (20)
- 一種用於減少人類皮膚中之色素沉著之局部組合物,其包含:(i)有效量之酪胺酸酶抑制劑,包含3,3'-硫二丙酸或其鹽或酯,及(ii)有效量之黑素體轉移抑制劑,包含菸鹼醯胺或其鹽或其黑素體轉移抑制衍生物,及(iii)化妝品上或皮膚學上可接受之媒劑。
- 如請求項1之組合物,其中該酪胺酸酶抑制劑包含3,3'-硫二丙酸。
- 如請求項1之組合物,其中該酪胺酸酶抑制劑包含具有結構式I之結構之3,3'-硫二丙酸之酯:
- 如請求項3之組合物,其中R1及R2各獨立地選自C1-20脂族烴基。
- 如請求項4之組合物,其中該酪胺酸酶抑制劑包含3,3'-硫代二丙酸二月桂酯。
- 如請求項1之組合物,其中該黑素體轉移抑制劑包含菸鹼醯胺或其鹽。
- 如請求項1之組合物,其中該菸鹼醯胺之黑素體轉移抑制衍生物具有結構式II之結構:
- 如請求項1之組合物,其中該3,3'-硫二丙酸或其鹽或酯與該菸鹼醯胺或其鹽或衍生物係依在以該組合物之總重量計約5:1(w/w)至約1:5(w/w)範圍內之比值存在。
- 如請求項1之組合物,其中該3,3'-硫二丙酸或其鹽或酯與該菸鹼醯胺或其鹽或衍生物係依該組合物之總重量計約10:1(w/w)之比值存在。
- 如請求項1之組合物,其中該酪胺酸酶抑制劑包含3,3'-硫二丙酸或其鹽,且該黑素體轉移抑制劑包含菸鹼醯胺或其鹽,且其中3,3'-硫二丙酸或其鹽係依在以該組合物之總重量計約0.1%(w/w)至約2.5%(w/w)範圍內之有效量存在,且菸鹼醯胺或其鹽係依在以該組合物之總重量計約0.01%(w/w)至約1%(w/w)範圍內之有效量存在。
- 如請求項10之局部組合物,其中有效量之3,3'-硫二丙酸或其鹽及有效量之菸鹼醯胺或其鹽共同減少之黑色素合成量比單獨使用其中任一組分時高出至少25%。
- 如請求項1之局部組合物,其中該化妝品上或皮膚學上可接受之媒劑包含油包水、水包油、聚矽氧包水、水包聚矽氧、聚矽氧包多元醇或多元醇包聚矽氧乳液,且進一步包含約0.001重量%至約20重量%之乳化劑。
- 一種減少人類皮膚中之色素沉著之方法,其包括將如請求項1之組合物局部塗覆至皮膚區域。
- 一種減少人類皮膚中色素沉著之方法,其包括將包含於化妝品上或皮膚學上可接受之媒劑中約0.01%至約10%(w/w)3,3'-硫二丙酸或其鹽或酯及約0.01%至約10%(w/w)菸鹼醯胺或其鹽或衍生物之組合物局部塗覆至皮膚,持續足以減少該皮膚出現色素沉著之時間。
- 如請求項14之方法,其中該組合物包含約0.01%至約2.5%(w/w)3,3'-硫二丙酸或其鹽及約0.01%至約2.5%(w/w)菸鹼醯胺或其鹽。
- 如請求項15之方法,其中該3,3'-硫二丙酸或其鹽及菸鹼醯胺或其鹽共同減少之黑色素合成量比單獨使用其中任一組分時高出至少25%。
- 如請求項15之方法,其中將該組合物至少每日一次塗覆至皮膚,持續一週或一週以上之時間期。
- 如請求項15之方法,其中將該組合物至少每日一次塗覆至皮膚,持續一週、四週或四週以上之時間期。
- 如請求項15之方法,其中皮膚遭受以下中之一或多者:皮膚黝黑、色素性皮膚變色、色素性胎記、色素過多、炎症後色素過多、損傷後色素過多、雀斑、老年斑、肝斑、太陽曬傷、曬黑、色素性痤瘡痕、疤痕、黑斑、黃褐斑、燒傷後疤痕、指甲染色、皮膚泛黃或黑眼圈。
- 一種減少皮膚中不需要之黑色素沉著之方法,其包括將包含約0.01%至約2.5%(w/w)3,3'-硫二丙酸或其鹽及約0.01%至約2.5%(w/w)菸鹼醯胺或其鹽之組合物局部塗覆至遭受不需要之色素沉著之皮膚區域。
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WO2012020070A2 (en) * | 2010-08-10 | 2012-02-16 | Behrooz Kasraee | Enhancement of the skin depigmentation |
CN103328561B (zh) * | 2011-01-21 | 2014-12-10 | 佳能株式会社 | 导电性橡胶弹性材料、充电构件和电子照相设备 |
-
2014
- 2014-02-26 CN CN201811371618.3A patent/CN109431828B/zh active Active
- 2014-02-26 CN CN201480010766.6A patent/CN105102073B/zh active Active
- 2014-02-26 CA CA2899611A patent/CA2899611A1/en not_active Abandoned
- 2014-02-26 PL PL14778546T patent/PL2969030T3/pl unknown
- 2014-02-26 EP EP14778546.3A patent/EP2969030B1/en active Active
- 2014-02-26 WO PCT/US2014/018692 patent/WO2014163896A1/en active Application Filing
- 2014-02-26 US US14/379,520 patent/US10117821B2/en active Active
- 2014-02-26 BR BR112015020196-2A patent/BR112015020196B1/pt active IP Right Grant
- 2014-03-05 TW TW103107515A patent/TWI679992B/zh active
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EP2969030A4 (en) | 2016-06-29 |
EP2969030A1 (en) | 2016-01-20 |
CN105102073B (zh) | 2019-06-04 |
BR112015020196B1 (pt) | 2020-09-29 |
PL2969030T3 (pl) | 2021-06-14 |
WO2014163896A1 (en) | 2014-10-09 |
US20160235646A1 (en) | 2016-08-18 |
WO2014163896A8 (en) | 2015-07-30 |
EP2969030B1 (en) | 2021-01-13 |
CN105102073A (zh) | 2015-11-25 |
TWI679992B (zh) | 2019-12-21 |
US10117821B2 (en) | 2018-11-06 |
HK1215410A1 (zh) | 2016-08-26 |
CN109431828B (zh) | 2021-11-12 |
BR112015020196A2 (pt) | 2017-07-18 |
CA2899611A1 (en) | 2014-10-09 |
CN109431828A (zh) | 2019-03-08 |
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