TWI448304B - 含順-6-壬烯醇及其衍生物之局部組合物及治療皮膚之方法 - Google Patents
含順-6-壬烯醇及其衍生物之局部組合物及治療皮膚之方法 Download PDFInfo
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- TWI448304B TWI448304B TW098144260A TW98144260A TWI448304B TW I448304 B TWI448304 B TW I448304B TW 098144260 A TW098144260 A TW 098144260A TW 98144260 A TW98144260 A TW 98144260A TW I448304 B TWI448304 B TW I448304B
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- A—HUMAN NECESSITIES
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Description
本發明大體上係關於局部施用於皮膚之含順-6-壬烯醇的組合物及該等組合物對皮膚提供益處,特定言之對人類皮膚提供抗衰老益處之用途。
金屬硫蛋白係一類富含半胱胺酸之低分子量蛋白質(例如,具有3500至14000Da範圍內之分子量(MW))。金屬硫蛋白具有經由其半胱胺酸殘基中之硫醇基結合生理性重金屬(例如Zn、Cu、Se)與外來異型生物質重金屬(例如Cd、Hg、Ag)之能力,半胱胺酸殘基幾乎佔其胺基酸殘基之30%。金屬硫蛋白參與生物系統中鋅之攝取、轉運及調節。結合鋅的位點一般富含半胱胺酸且通常結合三或四個鋅離子。在一些金屬硫蛋白中,組胺酸殘基亦參與鋅之結合及金屬/結合優先性之確定。藉由結合及釋放鋅,金屬硫蛋白調節體內鋅之水平。金屬硫蛋白將鋅離子自細胞之一部份協載至另一部份。如此,金屬硫蛋白成為細胞中鋅信號系統之關鍵組分。此系統在大腦中係尤其重要,其中鋅信號傳遞在神經細胞間及神經細胞內皆顯著。據信其對於調節抑癌蛋白p53亦重要。
金屬硫蛋白之半胱胺酸殘基可捕獲有害氧化劑自由基例如氫氧化物自由基。在此反應中,半胱胺酸被氧化成胱胺酸,及與半胱胺酸結合之金屬離子被釋放至介質。以此方式釋放之Zn可活化更多金屬硫蛋白。已建議此機制係金屬硫蛋白控制氧化壓力之重要機制。
已經多種方式報導了紫外輻射對金屬硫蛋白活性之影響。Yamada等人報導,以280nm之單色紫外線(UV)輻射的衍生自人類皮膚的被不同培養的三種細胞系,當由鎘、鋅或地塞米松(dexamethoasone)誘導時,顯示金屬硫蛋白之合成受到抑制。(參見Yamada,H.,Murata,M. Suzuki,K.,Koizumi,S.,Ultraviolet irradiation increases the sensitivity of cultured human skin cells to cadmium probably through the inhibition of metallothionein gene expression,Toxicol. Appl. Pharmacol. 200: 251-257(2004))。亦已報導無金屬硫蛋白的小鼠顯示對UVB損傷之耐受性降低。
Dubois等人之美國專利申請公開案2007/0071780(「Dubois」)描述一種包含「香氣增強劑調和物」之個人護理組合物,據說其係一種包含至少兩種高香氣值材料之芳香組合物,其改良傳統香料之可感覺香氣強度。順-6-壬烯醇係列為適合包含於該香氣增強劑調和物之材料。未揭示順-6-壬烯醇具有抗衰老益處。
Cawdell等人之PCT專利申請公開案WO2004/86866(「Cawdell」)描述一種用於控制昆蟲之系統,該系統包含一呈細長帶形式之基材,其上具有複數個沿該基材之第一表面以預定間隔分隔開之靶區域,每個靶區域各包含昆蟲引誘劑及/或昆蟲控制劑。Cawdell陳述,在一實施例中,每個靶區域間之沿該連續帶的間隔一般塗覆有黏著材料。該黏著材料據說用於輔助產品附著至農作物。或者,每個靶區域間之沿該連續帶的間隔據說係研磨材料或促進帶與農作物間摩擦之材料。Cawdell列出若干引誘劑的實例,包含Z-6-壬烯醇及E-6-壬烯醇。
Zander等人之PCT專利申請公開案WO2001/94438(「Zander」)描述在器官感覺上釋放活性芳香族醇的胺基甲酸酯化合物、一種用於製造該等胺基甲酸酯化合物之方法、及其於化妝品、膠質、塗料及塑膠組合物、及清潔產品、軟化劑、洗滌劑及洗碟機清潔劑組合物中之用途。Zander描述一實施例,其中該等胺基甲酸酯化合物具有化學式R[-NH-C(=O)-OR']n
其中n=1、2、3且R係衍生自具有1至30個碳原子之脂肪族、脂環族或芳香族單、雙、或三異氰酸鹽。Zander陳述,R'係衍生自具有化學式R'OH之醇類,其可選自由若干種醇組成之群,其包括順-6-壬烯醇、5-乙基-2-壬醇、6,8-二甲基-2-壬醇及2,2,8-三甲基-7(8)-壬烯-3-醇。
Light等人之PCT專利申請公開案WO2001/28327(「Light」)描述用於將鱗翅目害蟲自梨或蘋果隔離之兩性引誘劑,一種監測及控制蘋果蠹蛾及其他類種的鱗翅之方法,包括引誘及殺死、交配干擾或大量誘殺策略,及一種利用包含該等兩性引誘劑及或無殺蟲劑及/或信息素之調配物以控制害蟲之方法。Light陳述,該等引誘劑較佳具有下列結構式:
或
其中R及R1
係-CH3
、-CH2
CH3
或CH2
CH2
CH3
。Light亦列出若干包含(Z)-6-壬烯醇及(E)-6-壬烯醇之信息素之實例。
Ouchi等人之日本專利申請公開案JP2002-97291(「Ouchi」)描述一種來自藉由將微生物基因轉導入甜瓜組織所產生之甜瓜毛細管狀根部之芳香成份。該芳香成份據說係藉由將微生物基因轉導入甜瓜組織以產生毛細管狀根及藉由培養所產生的甜瓜毛細管狀根部以產生該芳香成份自身而獲得。Ouchi報導,該芳香成份可包含1-壬醛、6Z-壬烯醇及壬二烯醛。
因此本發明之一目標係提供新穎組合物及用於促進製造金屬硫蛋白之方法。本發明之另一目標係藉由以包含有效量之順-6-壬烯醇的化妝品組合物促進製造金屬硫蛋白而改良皮膚之整個外觀,包括處理、逆轉及/或預防衰老之跡象,例如皮膚皺紋。
上示論述部分僅更佳地理解該技藝遇到的問題本質及不應以任何方式視為對先前技術的認可,亦不應將文中引用的任何參考視組成「先前技術」的該參考文獻對本申請案之認可。
根據先前目標及其他,已驚人地發現順-6-壬烯醇係一種金屬硫蛋白之刺激劑及因此係一種對抗自然衰老及光老化皮膚之跡象的有益製劑。
在本發明之一態樣中,提供一種用於改良皮膚美觀之化妝品組合物,其化妝上可接受的媒介物中包括有效量之具有式I之結構的順-6-壬烯醇:
在本發明之另一態樣中,提供用於局部施用之化妝品組合物。該等化妝品組合物包含有效量之順-6-壬烯醇以處理、逆轉、改善及/或預防皮膚老化跡象。該等皮膚老化跡象非限製性包括下列:
(a) 細紋或皺紋之處理、減輕及/或預防;
(b) 皮膚毛孔大小之減小;
(c) 皮膚厚度、飽滿度及/或緊縮性之改良;
(d) 皮膚彈性及/或柔軟度之改良;
(e) 皮膚色調、光彩及/或純潔度之改良;
(f) 溶膠原及/或膠原製造之改良;
(g) 彈性蛋白之維護及重構的改良;
(h) 皮膚紋理之改良及/或蛋白質組織化之促進作用。
(i) 皮膚屏障修復及/或功能之改良;
(j) 皮膚外形之美觀程度的改良;
(k) 皮膚光澤及/或亮度之恢復;
(l) 皮膚中基本營養物及/或成份之補給;
(m) 因衰老及/或更年期影響的皮膚美觀之改良;
(n) 皮膚濕潤及/或水合之改良;
(o) 皮膚彈性及/或韌性之改良(例如增加及/或預防損失);
(p) 處理、減輕及/或預防皮膚下垂;及/或
(q) 處理、減輕及/或預防皮膚變色。
亦提供一種處理一或多個皮膚衰老跡象之方法,其一般包括將量足以有效提高金屬硫蛋白的順-6-壬烯醇施用至需要其之皮膚。
在本發明之另一態樣中,提供一種處理、逆轉、改善及/或預防人類皮膚之細紋或皺紋或下垂之方法,其一般包括將含有量足以提高金屬硫蛋白的順-6-壬烯醇之組合物局部地施用至需要其之皮膚,包括直接施用至皺紋或細紋。
參照下列詳細描述,將更好地理解本發明之該等及其他態樣。
除非另外提供,否則文中使用之所有術語意欲具有其平常意義。
如文中所使用,除非另外規定,否則「重量%」或「%wt」係指組分較組合物總重量(即,包括在施用至皮膚之前所添加的任何載劑、媒介物、溶劑、潤滑劑、填充劑或其他組分)之重量百分數。
本發明提供用於局部施用之組合物,其包含有效量之順-6-壬烯醇以處理、逆轉、改善及/或預防皮膚衰老跡象。該等皮膚衰老跡象非限定性包括下列:
(a) 細紋或皺紋之處理、減輕及/或預防;
(b) 皮膚毛孔大小之減小;
(c) 皮膚厚度、飽滿度及/或緊縮性之改良;
(d) 皮膚彈性及/或柔軟度之改良;
(e) 皮膚色調、光彩及/或純潔度之改良;
(f) 溶膠原及/或膠原製造之改良;
(g) 彈性蛋白之維護及重構的改良;
(h) 皮膚紋理之改良及/或蛋白質組織化之促進作用。
(i) 皮膚屏障修復及/或功能之改良;
(j) 皮膚外形之美觀程度的改良;
(k) 皮膚光澤及/或亮度之恢復;
(l) 皮膚中基本營養物及/或成份之補給;
(m) 因衰老及/或更年期影響的皮膚美觀之改良;
(n) 皮膚濕潤及/或水合之改良;
(o) 皮膚彈性及/或韌性之改良(例如增加及/或預防損失);
(p) 處理、減輕及/或預防皮膚下垂;及/或
(q) 處理、減輕及/或預防皮膚變色。
實際上,將本發明之組合物施用至需要處理之皮膚。即,因缺陷困擾或損失上述任意特性或否則因上述任意皮膚特性得到改良而受益的皮膚。
術語「皺紋」或「起皺紋」係指起細小皺紋及起較粗皺紋。細小皺紋或細紋係指皮膚表面上之表面紋及皺紋。較粗皺紋係指深皺紋,尤其係臉上及眼睛周圍之深紋/皺紋,包括表情紋例如皺眉紋及皺紋、額頭紋及皺紋、魚尾紋及皺紋、法令紋及嘴角紋及皺紋。額頭紋及皺紋係指額頭皮膚上之表面紋及/或深皺紋。魚尾紋及皺紋係指眼部周圍皮膚上之表面紋及/或深皺紋。嘴角紋及皺紋係指嘴周圍皮膚上之表面紋及/或深皺紋。可對紋數、持續時間及深度進行皺紋的評價。
皮膚彈性係指皮膚在變形後恢復其原樣及大小之彈性及恢復能力。皮膚之彈性可藉由捏壓試驗進行評估,其可因拉伸或擠壓皮膚而引起變形。
皮膚之變色包括離散性色素沉著,其一般稱為色素點或「老人斑」及斑點狀色素沉著。離散性色素沉著係更暗色素之清晰均勻區域及在皮膚上可以褐斑點或雀斑出現。斑點狀色素沉著係暗色斑痣,其在大小及形狀上比離散性色素沉著更大及更不規則。斑點狀色素沉著區域經陽光照射易變得更暗。
在某些較佳實施例中,本發明之組合物及方法係關於皮膚細紋及/或皺紋之預防、處理及/或改善。在此情況下,將組合物施用至需要處理之皮膚,此意指具有皺紋及/或細紋之皮膚。較佳地,將該等組合物直接施用至細紋及/或皺紋。該等組合物及方法適於處理任何皮膚表面上之細紋及/或皺紋,非限定性包括臉部、頸部、及/或手部皮膚。
用於處理與自然衰老或皮膚光老化相關之皮膚狀況的化妝品組合物之在化妝上可接受的媒介物中包含相當數量具有式(I)之結構的順-6-壬烯醇:
據信該組合物可有效增強金屬硫蛋白活性,期望其增大皮膚之光防護性質,因已藉由探查性活組織檢查驚人地發現在曝露至UV的皮膚中金屬硫蛋白表達下調(例如,18-25歲皮膚為53%及41-67歲皮膚為85%)。
根據本發明之組合物可以用於局部施用的多種形式調配及包含約0.0001%至約90重量%之順-6-壬烯醇,及較佳包含約0.001%至約25重量%,及更佳約0.01%至約10重量%。在更佳範圍內,組合物可包含約0.1%、0.25%、0.5%、0.75%或約1%至約5%、7.5%或約10%重量之範圍內的順-6-壬烯醇。該組合物將包含有效量之順-6-壬烯醇,其意指在局部施用至給定皮膚區域內足以利於產生金屬硫蛋白之量。
在一實施例中,該組合物基本上不含反-6-壬烯醇異構體或基本上不含具有除6-位之位置處具有雙鍵的壬烯醇異構體。「基本上不含」意指該等其他壬烯醇成份小於壬烯醇總量之5重量%,較佳小於2.5重量%,及更佳小於1重量%。在其他實施例中,該等組合物不含除順-6-壬烯醇之外的壬烯醇。
該組合物可以多種產品形式調配,諸如,例如洗劑、乳膏、漿液、噴霧、煙霧劑、餅狀物、軟膏、精華、膠、糊狀物、貼片、筆、濕紙巾、面膜、棒、泡沫、酏劑、濃縮液及其類似物,尤其用於局部投與。該組合物較佳係以洗劑、乳膏、軟膏或膠調配。
該等組合物可包含一種化妝上可接受的媒介物。該等媒介物可呈該技藝中已知的適於施用至皮膚之任何形式及可包含水(例如去離子水)、植物油、礦物油、酯例如棕櫚酸辛酯、肉豆蔻酸異丙基酯及棕櫚酸異丙基酯;醚例如二癸基醚及異山梨酯二甲醚;醇例如乙醇及異丙醇;脂肪醇例如十六烷醇、鯨蠟醇、硬脂醇及二苯基醇;異烷烴例如異辛烷、異十二烷及十六烷;矽酮油類例如環甲基矽酮、二甲基矽酮、二甲基矽酮交聯聚合物、聚矽氧烷及其衍生物,較佳係有機改性衍生物;烴類油例如礦物油、石蠟油、異二十烷及聚異丁烯;多元醇例如丙二醇、丙三醇、丁二醇、戊二醇及己二醇;蠟例如蜂蠟及植物性蠟;或前述物質之任何組合或混合物。
媒介物可包括水相、油相、醇、矽酮相或其混合物。化妝品上可接受的媒介物亦可包括乳液。適合乳液之非限定性實例包含油包水乳液、水包油乳液、水包矽酮乳液、矽酮包水乳液、水包蠟乳液、水/油/水三相乳液或具有乳膏、膠或微乳液外觀之類似物。該乳液可包含乳化劑,例如非離子性、陰離子性或兩性表面活性劑。
乳液之油相較佳具有一或多種有機化合物,包含軟化劑、保濕劑(例如丁二醇、丙二醇、甲基葡萄糖20環氧乙烷及丙三醇);其他可水分散性或可水溶性組分,包括增稠劑例如矽酸鎂鋁或羥烷基纖維素;膠凝劑,例如高MW聚丙烯酸,即CARBOPOL 934;及其混合物。該乳液可具有一或多種可乳化存在於該組合物中之多種組分之乳化劑。
適用於油相之化合物非限定性包括植物油、酯例如棕櫚酸辛基酯、肉豆蔻酸異丙基酯及棕櫚酸異丙基酯;醚例如二癸基醚;脂肪醇例如十六烷醇、十八烷醇及二十二醇;異烷烴例如異辛烷、異十二烷及異十六烷;矽氧油類例如聚二甲基矽氧烷、環矽氧及聚矽氧烷;烴類油例如礦物油、石蠟油、異二十烷及聚異丁烯;天然或合成蠟;及其類似物。適宜的疏水性烴類油可為飽和或不飽和,具有脂肪族特性及為直鏈或支鏈或含有脂環族或芳香族環。含油相可由單一油或不同油類之混合物組成。
烴類油包括具有6-20個碳原子,更佳10-16個碳原子之彼等物。代表性烴類包含癸烷、十二烷、十四烷、十三烷、及C8-20
異烷烴。石蠟烴類可以ISOPARS商標自Exxon購得及自Permethyl Corporation購得。此外,由Permethyl Corporation製造的商標名為Permethyl 99ATM之C8-20
石蠟烴類例如C12
異烷烴(異十二烷)亦認為係適合的。可購得的多種C16
異烷烴,例如異十六烷(商標名為Permethyl RTM)亦係適合的。較佳的揮發性烴類之實例包括聚癸烷例如異十二烷及異癸烷,包括例如Permethyl-99A(Presperse Inc.)及C7
-C8
至C12
-C15
異烷烴例如可購自Exxon Chemicals之Isopar系列。代表性烴類溶劑係異十二烷。
油相可包含一或多種蠟,包括例如米糠蠟、巴西棕櫚蠟、小冠椰子蠟、堪地裡拉蠟、褐煤蠟、甘蔗蠟、地蠟、聚乙烯蠟、Fischer-Tropsch蠟、蜂蠟、微晶蠟、矽酮蠟、氟化蠟及其任何組合。
非限製性乳化劑包括乳化蠟、乳化多元醇、聚醚多醇、聚醚、多元醇之單酯或二酯、乙二醇單硬脂酸鹽、丙三醇單硬脂酸鹽、丙三醇二硬脂酸鹽、含矽酮之乳化劑、大豆固醇、脂肪醇例如十六烷基醇、丙烯酸酯、脂肪酸例如硬脂酸、脂肪酸鹽及其混合物。較佳乳化劑包括大豆固醇、十六烷基醇、硬脂酸、乳化蠟、丙烯酸酯、含矽酮之乳化劑及其混合物。可用於本發明組合物之其他具體乳化劑包括但不限於一或多種下列物質:山梨聚糖酯、聚甘油基-3-二異硬脂酸鹽、C10-30
烷基丙烯酸酯交聯聚合物、聚二甲基矽酮PEG-7異硬脂酸酯、丙烯醯胺共聚物、礦物油、山梨糖醇酐單硬脂酸酯、山梨糖醇酐三硬脂酸酯、山梨糖醇酐倍半油酸酯、山梨糖醇酐單油酸酯、甘油酯例如單硬脂酸甘油酯及甘油單油酸酯、聚氧乙烯酚例如聚氧乙烯辛基酚及聚氧乙烯壬基酚、聚氧乙烯醚例如聚氧乙烯十六基醚及聚氧乙烯硬脂醯醚、聚氧乙二醇酯、聚氧乙烯山梨糖醇酐酯、二甲基矽酮共聚醇、聚甘油基酯例如聚甘油基-3-二異硬脂酸酯、甘油基月桂酸酯、硬脂醇聚醚-2、硬脂醇聚醚-10及硬脂醇聚醚-20、僅列舉幾個名稱。INCI Ingredient Dictionary and Handbook第11版2006中提供了另外的乳化劑,其所揭示之內容係以引用的方式併入本文中。
該等乳化劑一般係以約0.001%至約10重量%之量,特定言之係以約0.01%至約5重量%之量,及更佳係以約0.1%至約3重量%之量存在於組合物中。
該油相可包含一或多種揮發性及/或非揮發性矽酮油。揮發性矽氧油包括環狀及直鏈揮發性二甲基矽氧烷矽酮。在一實施例中,該等揮發性矽氧烷可包含環二甲基矽酮,包括四聚物(D4)、五聚物(D5)、及六聚物(D6)環甲基矽酮或其混合物。特別提及揮發性環甲基矽酮-六甲基環狀三矽氧烷、八甲基-環狀四矽氧烷、及十甲基-環狀五矽氧烷。適宜的二甲基矽酮可以Dow Corning 200Fluid之名購自Dow Corning及具有0.65至600,000厘斯或更高之黏度。適宜的非極性、揮發性液態矽酮油係揭示於美國專利第4,781,917號中,其全文係以引用的方式併入本文中。其他揮發性矽酮材料描述於Todd等人,「Volatile Silicone Fluids for Cosmetics」,Cosmetics and Toiletries,91:27-32(1976)中,其全文係以引用的方式併入本文中。直鏈揮發性矽酮一般具有25℃下之約小於約5厘斯之黏度,但環狀矽酮具有25℃下之約小於約10厘斯之黏度。具有不同黏度之揮發性矽酮之實例包括Dow Corning 200、Dow Corning 244、Dow Corning 245、Dow Corning 344及Dow Corning 345、(Dow Corning Corp.);SF-1204及SF-1202 Silicone Fluids(G.E. Silicones)、GE 7207及7158(General Electric Co.);及SWS-03314(SWS Silicones Corp.)。直鏈、揮發性矽酮包括低分子量聚二甲基矽氧烷化合物例如六甲基二矽氧烷、八甲基三矽氧烷、十甲基四矽氧烷及十二甲基五矽氧烷,僅列舉幾個名稱。
非揮發性矽酮油類一般包含聚烷基矽氧烷、聚芳基矽氧烷、聚烷芳基矽氧烷或其混合物。聚二甲基矽氧烷係較佳的非揮發性矽酮油類。該等非揮發性矽酮油類一般具有25℃下之約10至約60,000厘斯之黏度,較佳約10至約10,000厘斯,及更佳約10至約500厘斯,及於大氣壓下具有高於250℃之沸点。非限製性實例包括二甲基聚矽氧烷(二甲基矽酮)、苯基三甲基矽酮及二苯基二甲基矽酮。揮發性及非揮發性矽酮油類可視情況經多種官能基取代,例如烷基、芳基、胺基、乙烯基、羥基、鹵代烷基、烷芳基及丙烯酸酯根,僅列舉幾個實例。
矽酮包水乳液可由非離子性表面活性劑(乳化劑)乳化,諸如,例如聚二有機矽氧烷-聚氧化烯嵌段共聚物,包括美國專利第4,122,029號中所述之彼等物,其揭示內容以引用的方式併入本文中。該等乳化劑一般包含聚二有機矽氧烷主鏈,典型地係聚二甲基矽氧烷,其具有包含-(EO)m
-及/或-(PO)n
-基團之側鏈,其中EO係伸乙基氧及PO係1,2-伸丙基氧,該等側鏈一般經氫或低碳數烷基(例如C1-6
,一般係C1-3
)包覆或封端。其他適宜的矽酮包水乳化劑揭示於美國專利第6,685,952號中,其所揭示內容以引用的方式併入本文中。可購得的矽酮包水乳化劑包括可以商標名3225C及5225C FORMULATION AID自Dow Corning購得之彼等物、購自General Electric之SILICONE SF-1528、購自Goldschmidt Chemical Corporation(Hopewell,VA)之ABIL EM 90及EM 97、及OSI Specialties(Danbury,CT)出售的SILWET系列乳化劑。
矽酮包水乳化劑之實例包括但不限於二甲基矽酮PEG 10/15交聯聚合物、二甲基矽酮共聚醇、十六烷基二甲基矽酮共聚醇、PEG-15月桂基二甲基矽酮交聯聚合物、月桂基甲基矽酮交聯聚合物、環甲基矽酮及二甲基矽酮共聚醇、二甲基矽酮共聚醇(及)辛酸/癸酸甘油三酯、聚甘油基-4異硬脂酸酯(及)十六烷基二甲基矽酮共聚醇(及)己基月桂酸酯、及二甲基矽酮共聚醇(及)環戊矽氧烷。矽酮包水乳化劑之較佳實例非限製性包括PEG/PPG-18/18二甲基矽酮(商品名5225C,Dow Corning)、PEG/PPG-19/19二甲基矽酮(商品名BY25-337,Dow Corning)、十六烷基PEG/PPG-10/1二甲基矽酮(商品名Abil EM-90,Goldschmidt Chemical Corporation)、PEG-12二甲基矽酮(商品名SF 1288,General Electric)、月桂基PEG/PPG-18/18甲基矽酮(商品名5200 FORMULATION AID,Dow Corning)、PEG-12二甲基矽酮交聯聚合物(商品名9010及9011矽酮彈性體摻合物,Dow Corning)、PEG-10二甲基矽酮交聯聚合物(商品名KSG-20,Shin-Etsu)、二甲基矽酮PEG-10/15交聯聚合物(商品名KSG-210,Shin-Etsu)及二甲基矽酮PEG-7異硬脂酸酯。
該等矽酮包水乳化劑一般係以約0.001%至約10重量%之量,特定言之以約0.01%至約5重量%之量,及更佳係小於1重量%存在於組合物中。
該乳液之水相可包含一或多種其它溶劑,包括低碳醇類,例如乙醇、異丙醇及其類似物。揮發性溶劑亦可為化妝品上可接受的酯(例如乙酸丁酯或乙酸乙酯)、酮(例如丙酮或乙基甲基酮)、或其類似物。
含油相一般佔乳液總重量的約10%至約99%,較佳係約20%至約85%,及更佳係約30%至約70重量%,及水相一般佔整個乳液的約1%至約90%,較佳係約5%至約70%,及更佳係約20%至約60重量%。該水相一般包含約25%至約100%,更常見係約50%至約95重量%水。
在一些實施例中,組合物可包含多達約70重量%之揮發性溶劑,包括揮發性有機溶劑。具體而言,該組合物可包含多達約60%,較佳多達約50%,更佳多達約40%,及甚至更佳多達約30重量%之揮發性溶劑。在其他實施例中,該組合物可不含揮發性溶劑,包括揮發性有機溶劑。
組合物可包含脂質體。該等脂質體可包含其他添加劑或物質及/或可經改質以更具體地達到或停留在隨後進行投與的狀態。
該組合物可視情況包含其他化妝品活性劑及賦形劑,對擅長此項技術者顯而易見的包括,但不限於填充劑、乳化劑、抗氧化劑、表面活性劑、成膜劑、螯合劑、凝膠劑、增稠劑、軟化劑、保濕劑、濕潤劑、維生素、礦物質、黏度及/或流變改質劑、防曬劑、祛角質劑、脫色劑、視黃醛、荷爾蒙化合物、α-羥酸、α-酮酸、抗肺結核劑、抗真菌劑、抗微生物劑、抗病毒劑、止痛劑、油脂化合物、抗過敏劑、H1或H2抗組胺劑、消炎劑、抗刺激劑、抗腫瘤劑、免疫系統促進劑、免疫系統抑製劑、抗粉刺劑、麻醉劑、消毒劑、驅蟲劑、皮膚冷卻化合物、護膚劑、經皮滲透促進劑、潤膚劑、潤滑劑、芳香劑、著色劑、脫色劑、色素淡化劑、防腐劑(例如,DMDM乙內醯脲/碘代丙炔基丁基碳酸酯)、安定劑、藥劑、光穩定劑、中和劑(例如三乙醇胺)及其混合物。除前述物質外,本發明之化妝品組合物可含有任何其他用於處理皮膚病之化合物。
著色劑可包括例如有機及無機顏料及珠光劑。適宜的無機顏料包括,但不限於二氧化鈦、氧化鋯及二氧化鈰,以及氧化鋅、氧化鐵、氧化鉻及亞鐵藍。適宜的有機顏料包括鋇、鍶、鈣及鋁色澱及碳黑。適宜的珠光劑包含塗覆有二氧化鈦、氧化鐵或天然顏料之雲母。
可添加多種填充劑及其他組分。填充劑通常係以組合物總重量計之約0重量%至約20重量%,較佳約0.1重量%至約10重量%之量存在。適宜的填充劑非限製性包括矽石、經處理的矽石、滑石、硬脂酸鋅、雲母、高嶺土、尼龍粉末例如OrgasolTM
、聚乙烯粉末、TeflonTM
、澱粉、氮化硼、共聚物微球體例如ExpancelTM
(Nobel Industries)、PolytrapTM
(Dow Corning)及矽酮樹脂微珠體(TospearlTM
,來自Toshiba)及其類似物。
在本發明之一實施例中,本發明之組合物可包含芳香劑。芳香劑係可賦予組合物令人愉悅的香味之物質。典型的芳香劑包括自植物來源(即玫瑰花瓣、梔子花、茉莉花等)萃取之芳香族物質,可單獨或以任意組合使用以產生精油。或者,可製得醇類萃取物用於配合芳香劑。然而,因自天然物質獲取芳香劑之成本相對高,如今趨勢係使用合成製得的芳香劑,尤其係在大容量產品中。可視情況將一種或多種芳香劑以約0.001至約5重量%,較佳約0.01至約0.5重量%之量納入組合物中。在其他實施例中,本發明之組合物無香氣,此意指該組合物不含芳香劑,特定言之主要為提供香氣所添加的組分。
本發明組合物亦可含有一或多種驅蟲活性劑。該等活性劑包括但不限於N,N二乙基-間-甲苯醯胺(DEET)、丁基乙醯胺基丙酸乙酯(Merck Co.之IR3535)、羥乙基異丁基哌啶羧酸酯(1-哌啶羧酸)(Bayer KBR 3023)、對-薄荷烷-3,8-二醇、香茅油、大豆油、檸檬草油、天竺葵/香葉醇油、苦楝油及其他天然精油、對-薄荷烷-3,8-二醇或其任何混合物。該驅蟲活性劑可以基於組合物總重量之約0.05重量%至約90重量%,較佳約0.1重量%至約50重量%,及最佳約0.1重量%至約30重量%之量存在。在其他實施例中,本發明之組合物不含驅蟲活性劑,此意指該組合物不含驅蟲劑,例如,主要為驅蟲所常添加的組分。
在本發明之一實施例中,組合物可包含其它皮膚活性劑,例如但不限於植物製劑、角質溶解劑、剝離劑、角質細胞增殖增強劑、膠原酶抑製劑、彈性蛋白酶抑製劑、脫色劑、消炎劑、類固醇、抗粉刺劑、抗氧化劑、水楊酸或水楊酸鹽、硫代二丙酸或其酯、晚期糖基化終產物(AGE)抑製劑及α-羥基酸。
在一具體實施例中,組合物可包含至少一種其他植物製劑,諸如,例如植物製劑萃取物、精油或植物自身。適合的植物製劑非限製性包括自印度冷杉、兒茶、闊葉榆綠木、紫萁、印度楝樹、紫鉚、膠蟲樹、雪松、印度硬毛獼猴桃、孟加拉榕、甘草、冬青、總狀土木香、川芎、靈芝、粗糠柴、牛油果、檄樹、辣木、補血草、夾竹桃、補骨脂、大葉金花草、毗黎勒、番茄糖脂及其混合物之萃取物。
組合物可包含具有抗衰老益處之其它活性成份,因期望可因該等組合而增強改良效果。示例性抗衰老組分非限製性包括植物製劑(例如紫鉚萃取物)、硫代二丙酸(TDPA)及其酯、視黃醛(例如全反式視黃酸、9-順式視黃酸、植烷酸及其他)、羥酸(包括α-羥酸及β-羥酸)、水楊酸及水楊酸鹽、剝落劑(例如乙醇酸、3,6,9-三氧雜十一烷二酸等)、雌激素合成酶刺激性化合物(例如咖啡因及衍生物)、能夠抑製5α-還原酶活性之化合物(例如亞麻酸、亞油酸、非那雄胺、及其混合物)、屏障功能增強劑(例如神經醯胺、甘油酯、膽固醇及其酯、α-羥基及ω-羥基脂肪酸及其酯、等)、膠原酶抑製劑、及彈性蛋白酶抑製劑、僅擧幾個實例。
示例性視黃醛非限製性包括視黃酸(例如全反式或13-順式)及其衍生物、視黃醇(維生素A)及其酯,例如視黃醇棕櫚酸酯、視黃醇乙酸酯及視黃醇丙酸酯、及其鹽。
在另一實施例中,本發明之局部施用組合物亦可包含一或多種下列物質:皮膚滲透增強劑、軟化劑、皮膚豐滿劑、柔光劑、防曬劑、剝落劑及抗氧化劑。
軟化劑提供增強皮膚光滑性及減少細紋及粗皺紋出現之功能性益處。實例包括肉豆蔻酸異丙酯、礦脂、羊毛酸異丙酯、矽酮(例如甲基矽酮、二甲基矽酮)、油類、礦物油、脂肪酸酯、十六烷基己酸乙酯、C12-15
烷基苯甲酸酯、異丙基異硬脂酸酯、二聚亞油酸二異丙酯或其任何混合物。該軟化劑較佳係以組合物總重量之約0.1重量%至約50重量%存在。
皮膚豐滿劑係作為皮膚之膠原蛋白增強劑。適宜且較佳的皮膚豐滿劑之實例係棕櫚醯低聚肽。其他皮膚豐滿劑係膠原蛋白及/或其他葡萄胺聚糖(GAG)增強劑。若存在,皮膚豐滿劑可佔該組合物總重量之約0.1重量%至約20重量%。
散光劑係一種改變皮膚表面視光性之顆粒,導致例如細紋及皺紋視覺上模糊及柔化。可用於本發明之散光劑實例包括但不限於氮化硼、雲母、尼龍、聚甲基丙烯酸甲酯(PMMA)、聚胺基甲酸酯粉末、絹雲母、矽石、矽酮粉末、滑石、聚四氟乙烯、二氧化鈦、氧化鋅、或其任何混合物。當存在時,該散光劑可佔組合物總重量之約0.01重量%至約20重量%。
亦可包含用於保護皮膚免受損傷性紫外線傷害之防曬劑。較佳防曬劑係具有寬UVB及UVA保護範圍之彼等物,例如奧克立林、阿伏苯宗(Parsol 1789)、甲氧基肉桂酸辛酯、水楊酸辛酯、氧苯酮、甲基水楊醇、苯甲酮、樟腦衍生物、氧化鋅及二氧化鈦。當存在時,該防曬劑可佔組合物之約0.01重量%至約70重量%。
適合的剝落劑包括例如α-羥基酸、β-羥基酸、草酸、二草酸及其衍生物,例如其酯類、酸酐及鹽。適合的羥基酸包括例如乙醇酸、乳酸、蘋果酸、酒石酸、檸檬酸、2-羥基鏈烷酸、扁桃酸、水楊酸及其衍生物。較佳的剝落劑係乙醇酸。當存在時,該剝落劑可佔組合物之約0.1重量%至約80重量%。
抗氧化劑值得一提之功能在於自皮膚清除自由基以保護皮膚免受環境侵害。可用於本發明組合物之抗氧化劑實例包括具有酚羥基官能團之化合物,例如抗壞血酸及其衍生物/酯、α-羥基酸、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)、沒食子酸衍生物(例如沒食子酸丙酯)、番茄紅素、還原酸、迷迭香酸、單寧酸、四氫薑黃素、生育酚及其衍生物(例如醋酸生育酚酯)、尿酸或其任何混合物。其他適合的抗氧化劑係具有一或多個硫醇官能團(-SH)之彼等物,其為還原態或非還原態,例如谷胱甘肽、硫辛酸、巰基乙酸及其他巰基化合物。抗氧化劑可為無機物,例如重亞硫酸鹽、偏亞硫酸氫鹽、亞硫酸鹽、或其他含硫的無機鹽及無機酸。本發明之組合物可包含較佳佔該組合物總重量之約0.001重量%至約10重量%,及更佳約0.01重量%至約5重量%之抗氧化劑。
其他常見添加劑包括:維生素,例如生育酚及抗壞血酸、維生素衍生物例如抗壞血酸基單棕櫚酸酯、增稠劑例如羥烷基纖維素、凝膠劑、結構化劑例如膨土、綠土、矽酸鎂鋁及矽酸鋰鎂、金屬螯合劑例如EDTA、顏料例如氧化鋅及二氧化鈦、著色劑、軟化劑及濕潤劑。
組合物最佳基本上不含具有強氧化勢之組分,包含例如有機或無機過氧化物。「基本上不含」該等組分意指存在量不足以對順-6-壬烯醇增強金屬硫蛋白活性在測量上產生影響。在一些實施例中,以莫耳計,其相對於順-6-壬烯醇之量小於1%。
在一實施例中,含順-6-壬烯醇之本發明組合物可具有約1至約8之間的pH。在一些實施例中,該組合物之pH為酸性,即小於7.0,且較佳於約2至約7之間,更佳係於約3.5至約5.5之間。
本發明提供一種用於處理老化皮膚之方法,其藉由於受影響區域上局部施用含順-6-壬烯醇之組合物,較佳係於化妝品上可接受的媒介物中,進行一段時間以足以減少、改善、逆轉或預防皮膚老化跡象。此方法特別用於處理皮膚光老化及自然老化跡象。具體而言,期望此方法用於處理經UV損傷的皮膚。
一般而言,狀況及/或美觀度之改良係選自由下列組成之群:減少自然老化、光老化、荷爾蒙老化及/或光化學老化之皮膚跡象;預防及/或減少細紋及/或皺紋之出現、減少面部細紋及皺紋、面頰、額頭之皺紋、兩眼間縱紋、眼部上方及嘴部周圍的橫紋、嘴角紋及極深的皺紋或皺痕之明顯性;預防、減少、及/或縮小細紋及/或皺紋之出現或深度;改良眼眶下細紋及/或眼窩細紋之出現;減少魚尾紋之出現;使皮膚尤其係老化皮膚復原及/或新生;降低皮膚脆弱性;預防及/或逆轉葡萄胺聚糖及/或膠原蛋白之損失;改善雌激素失調之影響;預防皮膚萎縮;預防、減少及/或處理色素沉著過度;使皮膚變色最小化;改善膚色、光澤、純潔度及/或緊縮性;預防、減少及/或改善皮膚下垂;改良皮膚緊實度、豐滿度、柔軟度及/或柔性;改良溶膠原及/或膠原蛋白產生;改良皮膚紋理及/或促進重織構化;改良皮膚屏障修復及/或功能;改良皮膚外觀;恢復皮膚光澤及/或亮度;使疲勞及/或壓力性皮膚跡象最小化;抵抗環境壓力;補充皮膚中因老化及/或更年期減少之成份;改良皮膚細胞間聯係;增加細胞繁殖及/或加倍;增加因老化及/或更年期降低之皮膚細胞代謝;減緩細胞老化;改良皮膚濕潤性;增加皮膚厚度;增加皮膚彈性及/或彈力;增強剝落;改良微循環;減少及/或預防橘皮組織形成;及其任何組合。
無意受任何特定理論束縛,據信本發明之組合物藉由刺激金屬硫蛋白增強及改良皮膚外觀。
一般一天一次、二次或三次將該組合物施用至皮膚,歷經需達到所期望的抗老化效果之時間。療程可包含每日施用並持續至少一星期、至少兩星期、至少四星期、至少八星期或至少十二星期。亦期望長期療程。
將順-6-壬烯醇活性組分局部地施用至「需要其之個人」,其意指欲從減少皮膚損傷或老化之可視跡象而受益之個人。在一具體實施例中,該順-6-壬烯醇組分係於醫藥上、生理上、化妝品上及皮膚病學上可接受的媒介物、稀釋劑或載劑中提供,其中將該組合物局部施用於皮膚之受影響區域並以有效改善皮膚狀況及美觀之量存留於該受影響區域。
在一實施例中,用於處理細紋及皺紋之方法包括將本發明之順-6-壬烯醇組合物局部施用至需要其之個人的皮膚,例如以一定量直接局部施用至細紋及/或皺紋且持續足以減少細紋及/或皺紋之嚴重程度或預防或制止新細紋及/或皺紋形成之時間。可對組合物於細紋及皺紋形成或出現之影響進行質評(例如目測)或量評,例如由顯微鏡或計算機輔助測量皺紋形態(例如,每單位面積皮膚之皺紋的數目、深度、長度、面積、體積及/或寬度)。此實施例包括處理手、手臂、腿、頸、胸部及包括額頭之面部的皮膚上的老化皮膚(包含皺紋)。
亦期望本發明組合物用於處理薄皮膚,其藉由將該組合物局部施用至需要其之個人的薄皮膚處。「薄皮膚」用於包括因自然老化、更年期或光損傷而變薄的皮膚。在一些實施例中,該處理係用於男性之薄皮膚,而其他實施例處理更年期前或更年期後的女性之薄皮膚,據信男性及女性,特定言之處於不同階段的女性,其等皮膚隨年齡而變薄程度不同。
可預防性地利用本發明之方法以預防無明顯皮膚老化跡象之患者,最常見之小於25歲之個人所涉及的老化。該方法亦可逆轉或處理25歲以上患者常見的老化跡象。
在含有適當培養基之96孔組織培養處理板中培養正常人類真皮纖維母細胞。製備順-6-壬烯醇之乙醇儲備溶液。在含10% CO2
之37℃潮濕培養箱中,以經生長培養基稀釋之試驗材料或乙醇媒介物對照品處理細胞。培養之後,移除每個板的生長培養基及將100μl裂解緩衝液加入孔中及置於含10% CO2
之37℃培養箱中30分鐘。在培養結束時,將細胞收集於冷凍板中及置於-80℃冷凍裝置中直至分析。使用應用分支DNA技術之Panomics之多重分析系統分析經處理的金屬硫蛋白2A(MT2A)中mRNA的變化。藉由比較試驗與媒介物對照品之結果,計算MT2A中mRNA的增長百分比。經0.01%或0.001%之順-6-壬烯醇處理之纖維母細胞顯示金屬硫蛋白2A中mRNA水平分別增長96%及97%。所報導結果有統計學意義(p<0.05)。
表1中提供用於局部施用至皮膚之含順-6-壬烯醇之化妝品組合物。
據信該等組合物對處理、逆轉、改善及/或預防皮膚老化跡象係有效的,具體而言,據信該等組合物減少皮膚出現細紋及皺紋。將表1之組合物施用至需要處理之皮膚,其意指需要抗老化益處之皮膚,及特定言之具有皺紋及/或細紋之皮膚。可直接將該等化妝品組合物施用至細紋及/或皺紋。可施用示例性組合物以處理、逆轉、改善及/或預防皮膚任何表面上之細紋及/或皺紋,非限製性包括面部、頸及/或手部之皮膚。
每天一次、二次或三次將該化妝品組合物施用至皮膚,歷經需達到所期望的抗老化效果之時間,其療程可包含每日施用並持續至少一星期、至少兩星期、至少四星期、至少八星期或至少十二星期。另,示例性化妝品組合物可用於長期治療皮膚、細紋及/或皺紋。
專利申請案與公開案中涉及的所有參考之全文係以引用的方式併入文中,且引用程度就如同已特定地及個別地將各個公開案或專利或專利申請案之全文以引用的方式併入一般。可在未脫離本發明主旨及範圍下進行若干修改與變化,其對擅長該技術者係顯而易見的。文中所述的具體實施例僅以實例的方式給出,且本發明僅由隨附的專利請求範圍中條件及此等專利請求範圍所授予的等效物之全部範圍限制。
Claims (21)
- 一種用於賦予人皮膚抗老化益處之方法,其包括將於化妝品上可接受的媒介物中之含順-6-壬烯醇的組合物局部施用於需要其之個人的皮膚,該組合物包含基於該組合物總重量計自0.0001重量%至90重量%之呈單離或純化形式之順-6-壬烯醇,以有效賦予皮膚抗老化益處。
- 如請求項1之方法,其中該皮膚遭受皮膚光老化。
- 如請求項1之方法,其中該抗老化益處係選自由下列組成之群:(a)細紋或皺紋之處理、減輕及/或預防;(b)皮膚毛孔大小之減小;(c)皮膚厚度、飽滿度及/或緊縮性之改良;(d)皮膚彈性及/或柔軟度之改良;(e)皮膚色調、光彩及/或純潔度之改良;(f)溶膠原及/或膠原蛋白製造之改良;(g)彈性蛋白之維護及重構的改良;(h)皮膚紋理之改良及/或重織構化之促進;(i)皮膚屏障修復及/或功能之改良;(j)皮膚外形之改良;(k)皮膚光澤及/或亮度之恢復;(l)皮膚中基本營養物及/或成份之補給;(m)因更年期影響的皮膚美觀之改良;(n)皮膚濕潤之改良; (o)皮膚彈性及/或韌性之改良;或(p)處理、減輕及/或預防皮膚下垂;及/或(q)處理、減輕及/或預防皮膚變色。
- 如請求項3之方法,其中該抗老化益處係細紋或皺紋之處理、減少及/或預防。
- 如請求項3之方法,其中該抗老化益處係皮膚下垂之處理、減少及/或預防。
- 如請求項3之方法,其中該抗老化益處係皮膚變色之處理、減少及/或預防。
- 如請求項3之方法,其中該抗老化益處係皮膚彈性之改良。
- 如請求項1之方法,其中該順-6-壬烯醇係以足以增強金屬硫蛋白活性之量存在。
- 如請求項1之方法,其中該順-6-壬烯醇係以基於該組合物總重量計之0.001重量%至25重量%之量存在。
- 如請求項9之方法,其中該順-6-壬烯醇係以基於該組合物總重量計之0.01重量%至10重量%之量存在。
- 一種處理皺紋及/或細紋之方法,其包括:將於化妝品上可接受的媒介物中之組合物局部施用於需要其之個人之皮膚上的皺紋及/或細紋,歷經足以減少該等皺紋或細紋之嚴重程度的時間,該組合物包含基於該組合物總重量計自0.0001重量%至90重量%之呈單離或純化形式之順-6-壬烯醇。
- 一種提供人類皮膚益處之方法,其包括: 將於化妝品上可接受的媒介物中之組合物局部施用至受UV輻射而損傷之皮膚區域,歷經足以改良皮膚美觀之時間,該組合物包含基於該組合物總重量計自0.0001重量%至90重量%之呈單離或純化形式之順-6-壬烯醇。
- 一種用於賦予皮膚抗老化益處之局部組合物,其包含:基於該組合物總重量計自0.0001重量%至90重量%以有效賦予皮膚抗老化益處之量的呈單離或純化形式之順-6-壬烯醇,至少一種其他皮膚活性劑,及一種化妝品上可接受的媒介物,該化妝品上可接受的媒介物包含經乳化劑穩定之油包水或水包油乳液。
- 如請求項13之局部組合物,其中該其他皮膚活性劑係選自由植物製劑、角質溶解劑、剝離劑、角質細胞增殖增強劑、膠原酶抑製劑、彈性蛋白酶抑製劑、脫色劑、消炎劑、類固醇、抗粉刺劑、抗氧化劑、水楊酸或水楊酸鹽、硫代二丙酸或其酯、晚期糖基化終產物(AGE)抑製劑及α-羥基酸組成之群。
- 如請求項14之局部組合物,其中該其他皮膚活性劑係α-羥基酸。
- 如請求項14之局部組合物,其中該其他皮膚活性劑係抗氧化劑。
- 如請求項14之局部組合物,其中該其他皮膚活性劑係彈性蛋白酶抑製劑。
- 如請求項14之局部組合物,其中該其他皮膚活性劑係膠 原酶抑製劑。
- 如請求項13之局部組合物,其中該順-6-壬烯醇係以基於該組合物總重量計之0.001重量%至25重量%之量存在。
- 如請求項19之局部組合物,其中該順-6-壬烯醇係以基於該組合物總重量計之0.01重量%至10重量%之量存在。
- 如請求項13之局部組合物,其進一步包含防曬劑。
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