TW201536343A - 用於皮膚抗老化處理之組成物 - Google Patents
用於皮膚抗老化處理之組成物 Download PDFInfo
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- TW201536343A TW201536343A TW103126323A TW103126323A TW201536343A TW 201536343 A TW201536343 A TW 201536343A TW 103126323 A TW103126323 A TW 103126323A TW 103126323 A TW103126323 A TW 103126323A TW 201536343 A TW201536343 A TW 201536343A
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Abstract
本發明係關於一種組成物，其包含蛇麻(Humulus lupulus)萃取物、結合玻尿酸以及C1-C4烷醇，並且用於人類皮膚之抗老化處理。本發明之新穎組成物係藉由局部投予來使用。
Description
本發明係關於一種組成物，其包含蛇麻(Humulus lupulus)萃取物、結合玻尿酸以及C1-C4烷醇，並且用於人類皮膚之抗老化處理。本發明之新穎組成物係藉由局部投予來使用。
老化的過程就是細胞老化之生理結果以及相對應之對應力反應的能力下降。這種不可逆的過程會導致體內的一些變化：其中之一係與臉部皺紋的出現有關。
皮膚係由兩個主要的層所構成：外層係為主要由角質細胞所構成之表皮層，負責形成對抗環境損害(病原體、熱、紫外線輻射、以及水份流失)的屏障。內層之真皮層包含結締組織，其係由例如膠原蛋白(負責皮膚緊實度)、彈性纖維(負責皮膚彈性)以及細胞外基質(結構成份)之結構成分所構成的。還有第三層之皮下組織層，其包含為身體提供絕緣作用(insulation)的脂肪細胞。
皺紋係損害生物分子功能的醣化過程所導致之皮膚的折疊、隆起或皺褶(Danby FW,"Nutrition and aging skin：sugar and glycation",Clin Dermatol 2010,28(4)：409-411)。老化過程並不是皺紋出現的唯一原因，
其他可能促進皺紋生成的因素為吸煙、太陽曝曬、皮膚類型、環境因素、以及基因遺傳(Demierre MF et al,“Public knowledge,awareness,and perceptions of the association between skin aging and smoking”,J Am Acad Dermatol,1999,41(1)：27-30)。
皮膚皺紋的形成係取決於缺乏膠原蛋白，或是其之變形、變薄、及/或破裂，或是在皮膚的某些區域(尤其是臉部)中的拉伸和重複延伸，而導致的皮膚結構的損壞(Fisher GJ,“The Pathophysiology of Photoaging of the Skin”Cutis,2005,75(2S)：5-9)。同時缺乏彈性蛋白在此一過程中也扮演重要的角色。彈性蛋白的減少以及其所導致之彈性喪失，造成皮膚量增加以及例如雙下巴現象的出現。在皮膚架構中之所有此等變化的組合，會導致皺紋的出現，並且皺紋的性質是依皮膚和肌肉收縮的性質而定。這種退化過程的結果，導致皮膚的脆弱性增強、表皮可獲得的營養物質量減少、干擾正常皮膚修復過程，因而將帶來更為顯著之皺紋生成與鬆弛的過程。
習慣性的臉部表情以及因而導致之肌肉的長久性收縮，造成皮膚由於如上述的組織損耗而產生皺紋。此外，重力的作用亦為皺紋出現以及皮膚鬆弛的原因。其會引起下顎垂肉和眼瞼下垂。
因此，老化是一種會影響皮膚之不可逆的過程，由於該等層中所含之結構物質的減少，或是該等纖維(主要是膠原蛋白)之再成形並不完全，以及其它之多因素問題，而致使皺紋形成。
主要包括膠原蛋白纖維與彈性蛋白之損耗組織的再生，應為處理與避免皺紋之最佳標的。
在該技術領域中，有很多可藉由醫藥、外科手術、以及化妝的解決方案，用於改善皺紋的處理方法。這些處理方式之目的是要改變老化膠原蛋白之性質、使皮膚緊實、填補皮膚中之凹陷部分、或是使導致皮膚生成皺褶之肌肉麻痺。
在藥物處理中，包含：維生素A酸(類視網醇(retinoid)類)，其增進皮膚細胞的更新，但是此等可能會導致發紅、脫皮以及全身不適(general discomfort)；α-羥酸，其滲透進入皮膚層表面，只能產生些微的改善，並且會造成輕微和暫時性的刺激；抗老化精華液(serum)，其刺激皮膚，以重建真皮層中膠原蛋白和彈性蛋白網絡來致使皮膚結構更新，以改善皮膚的彈性並撫平皺紋。然而此等之缺點係關於成本，以及由動物來源所獲得之該組成物的實際化合物為何，通常也都沒有明確說明。
在外科手術之技術領域中，也有很多的相關技術：磨皮(dermabrasion)和雷射磨皮(laser resurfacing)，其等係分別藉由旋轉研磨儀器(rotating instrument)與雷射來研磨皮膚。即便所有的這些處理方法都可以得到良好的改善效果，此等也會產生顯著的副作用，包括產生疤痕與皮膚顏色之永久性變化。
整形外科手術(外科整容)，其包含：注射肉毒桿菌毒素來放鬆臉部肌肉以讓皺紋線條消失，以填料
(由膠原蛋白或玻尿酸以及鈣羥基磷灰石(calcium hydroxyapatite)製成，或是轉移自體脂肪)來增加體積以撫平皺紋和皺褶；熱與射頻為其他在進行老化處理時提供良好改善效果之技術。這些改善效果會持續幾個月，之後必須重複進行以維持改善效果。又，相對於組織再生過程，外科手術僅作為美觀的方法，而不具有皮膚回春的涵義。
在化妝品中，包含：表面或深層換膚產品，其用於平滑細紋與疤痕；微晶磨皮霜(microdermabrasion)，其係作為溫和去角質劑(exfoliating agent)。相對於組織再生，這兩者大多僅是試圖藉由維持最表面之皮膚層，來改善皮膚凹陷之情況。
抗氧化劑可以提供防曬、中和導致膠原蛋白分解的自由基：藉由這種機制，抗氧化劑對於預防皺紋形成的進一步惡化可說是非常重要。最後，保濕劑可以讓皺紋看起來暫時不太顯著，並保持皮膚濕潤。
作為結論，用來處理與預防皺紋形成之最佳產品，應該具有以下功效：1)使組織(主要是膠原蛋白)再生、2)對抗氧化作用、3)滋潤皮膚。
臨床和視覺評估(鼻唇溝(nasolabial folds)和魚尾紋的皺紋層級、顴骨區域下垂度、表面微起伏度、皮膚暗沉度、皮膚緊實度)以及工具評估，都是用來測定抗老化處理之效果時，所需要的代表性方法(Grove GL et al,Optical Profilometry：an objective method for quantification of facial wrinkles J Am Acad Dermatol,21：
631-637,1989)。鼻唇溝以及眼睛周圍的區域之皺紋的等級，是藉由兩種參考的臨床和照片標度尺，來確認是否存在有該等級的皺紋來進行認定，將結果計分為0(無皺紋)至7(非常顯著之皺紋)。同樣地，頦下下垂度也依據臨床照片標度尺，而計分為0(無下垂-很普通的瓜子臉)到5(非常顯著的下垂-非常不正常的瓜子臉)(Monheit GD et al.Development and validation of a 6-point grading scale in patients undergoing correction of nasolabial folds with collagen implant.Dermatol Surg 2010；36：1809-1816)。表面微起伏度同樣是依據照片標度尺，以1(非常規則)至4(非常不規則)的參考級分來進行評估。
整體臉部的皮膚暗沉度，係以1(具有光澤的皮膚)至4(非常不具有光澤的皮膚)的級分來評估光澤；且皮膚緊實度，是依據0(非常大量)至4(非常微量)的級分，來評估臉頰(顴骨區域)之皮膚抗捏夾性、抗拉伸性、在被捏夾後的恢復性。
在本技術領域中，我們將在以下的內容中看到，蛇麻(Humulus lupulus；通常稱為啤酒花)雖然需要在一個非常高的含量下使用，但是其係已知之抗皺劑。其係大麻科植物中之一個物種，為很多的啤酒以及其他釀造飲料之主要成分。啤酒花球花中包含樹脂苦味質(resinous bitter principles)(5-30%)，主要是α-苦酸(葎草酮(humulone)2-10%)和β-苦酸(蛇麻酮(lupulone)2-16%)以及此等之氧化降解產物(2-甲基-3-丁烯-2-醇)；多酚縮合單寧類(2-4%)；揮發油(0.35-1.0%)，主要為單萜和倍
半萜(β-石竹烯、菌綠烯、蛇麻烯、β-月桂烯)；查耳酮類(黃腐酚(xanthohumol))；類黃酮類(番鬱金黃素、槲皮素、芸香苷)；酚酸類；以及胺基酸類(Bradley,1992；Bruneton,1995；ESCOP,1997；Leung and Foster,1996；Newall et al.,1996；Wichtl and Bisset,1994)。為了藥學上之用途，植物萃取物係以此等之生產程序(欲被萃取之草藥狀態、溶劑、萃取條件)以及此等之規格來界定，而一貫被製備為液態(例如液體萃取物與酊劑)、半固態(軟萃取物以及油性樹脂)或是固態(乾燥萃取物)。萃取物係使用水、乙醇、或是其它符合相關藥典專論的合適有機溶劑，而藉由適合的方法(例如浸漬、滲濾(percolation))來加以製備。欲進行萃取之草藥可接受例如酵素去活性、研磨、或脫脂之初步處理。(Ph.Eur.7.0 04/2008：0765)。
啤酒花在歷史上已被證實具備藥草用途，其中此等主要是用於此等已知的舒緩、鎮靜、滋補以及身體與心靈上的安定(Schiller et al,Sedating effects of Humulus lupulus L.extracts,Phytomedicine.2006；13(8)：535-41)。
WO2007/085327A1揭露將蛇麻萃取物用於陰道用途上，來預防停經後婦女的陰道乾燥，其儘可能使用低濃度的蛇麻萃取物，以避免任何前雌激素效應(pro-estrogenic effect)。在一份文獻中已經披露使用蛇麻來減輕皮膚老化跡象，並使得皺紋不明顯或消失，其中從蛇麻中分離之類黃酮類之一的黃腐酚具有兩種不同濃
度(0.1%和1%)，結果有效地改善皮膚結構與緊實度(Philips N et al,“Direct inhibition of elastase and matrixmetalloproteinases and stimulation of biosynthesis of fibrillar collagens,elastin,and fibrillins by xanthohumol”,J Cosmet Sci,2010,61(2)：125-32)。黃腐酚佔蛇麻藥物總含量之1%(Milligan SR et al,“The endocrine activities of 8-prenylnaringenin and related hop(Humulus lupulus L.)flavonoids”J Clin Endocr Metab,2000,85(12)4912-5)，而依據Philips的文獻中的兩種有效濃度都非常的高，且在抗皺霜等中，藉由使用母酊劑(mother tincture)或萃取物並不能達到該等濃度。為了達到在該引用技術中對於皺紋有效用之濃度，就必須採用複雜而昂貴的萃取方法。
另一個用來對抗皺紋之成分是玻尿酸。其係一種人體中的天然成分，可在上皮和結締組織中發現。其提供三種主要功能：保護關節之間的軟骨不受機械性損耗、使此等維持含水、並控制細胞的遷移。其藉由幫助白血球對抗多種類型的感染，而在刺激免疫反應上亦扮演重要的角色。由於其有效的生物水化性質以及其再生特性，玻尿酸在許多抗老化面霜和精華液中被用來作為主要成分，雖然為了實質有效其濃度必須要等於或高於0.1%(Pavicic T,Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment,J Drugs Dermatol 2011,10：990-1000)。
乙醇是廣泛應用於家庭與工業中，最為常見的有機溶劑。藉由使用乙醇或是例如低級烷醇的其他低分子量醇類，也可以獲得類似的效果；該低級烷醇例如丙醇、異丙醇等。由於乙醇以及其他低級烷醇，具有藉由將微生物蛋白質變性、將其脂質溶解來殺死微生物的能力，而可以有效地對抗許多種細菌和真菌，因此係廣泛應用於例如醫療用紙巾以及抗菌乾洗手凝膠等，直接與人體皮膚接觸之產品中。相反地，乙醇以及丙醇或異丙醇，並不建議用於皮膚回春/抗皺的組成物中，因為此等之脂質溶解效果和脫水效果，可能會由於使皮膚變薄及使皮膚硬化，而使得皮膚老化及皺紋生成的情況更嚴重。
本發明驚奇地發現，例如乙醇之C1-C4烷醇，可以與蛇麻以及玻尿酸產生協同作用，並且在施用於皮膚上時，由於膠原蛋白再生、抗氧化效果、以及保濕，而有助於達成抗老化的效果。
此一協同作用組合的另一項優點是，其在主要成分處於非常低的濃度下，例如在蛇麻萃取物的重量至多達到15%時仍具有活性，因此含有比Philips N等人的文獻中所揭露者還要來得低之黃腐酚劑量，可避免任何雌激素效應。同樣地，該組合物在重量至多達5%之非常低濃度的玻尿酸下仍具有活性，因此可以節省此一成分的高成本。
本發明之標的係為一種包含C1-C4烷醇、結合蛇麻萃取物和玻尿酸的組成物，以及其作為人類皮膚之抗老化處理的用途。
為了要進行本發明之抗老化處理，低濃度的蛇麻係與低濃度的玻尿酸，以及較佳為乙醇之C1-C4烷醇的組合，係以半固體或液體配方的形式來進行局部投予；此等配方可以是溶液、乳液或懸浮液、乳霜、凝膠、精華液和軟膏的形式。此等係特別適合藉由直接施用在臉部表面上，以達成抗老化效果。
這種蛇麻萃取物可以是液態、半固態或是固態的萃取物，較佳為液態萃取物，更佳為由新鮮植物球花所製成之所謂「母酊劑」的酊劑(Ph.Eur.7.3,01/2012：2029)。這種萃取物可以藉由將蛇麻的新鮮雌性球花，於室溫下(較佳為20~25℃)，浸離於水和乙醇的溶液中20天至30天而獲得。水份通常係以相對於乙醇之重量比35.0%至55.0%的比例來使用。
蛇麻的萃取物可以0.1%至15%，更佳為0.2%至5%，最佳為0.5%至2.5%之重量百分比濃度來存在。
玻尿酸可以其本身，或是以藥學上可接受之鹽類或酯類的形式來使用。藥學上可接受的鹽類，可以選自於鈉鹽、鉀鹽、鈣鹽或具有天然胺基酸(如離胺酸、精胺酸、甲硫胺酸、或天冬胺酸)的鹽類。藥學上可接受的酯類，則可以選自於玻尿酸抗壞血酸酯、玻尿酸棕櫚醯酯、玻尿酸芐酯、丁醯鈉玻尿酸酯(sodium butyroyl hyaluronate)、丁醯/甲醯鈉玻尿酸酯(sodium butyroyl/formoyl hyaluronate)。
較佳之玻尿酸酯類是丁醯鈉玻尿酸酯、玻尿酸棕櫚醯酯、以及玻尿酸抗壞血酸酯。
玻尿酸或是其藥學上可接受的鹽類或酯類，可以0.01%至5%，更佳為0.025%至4%，最佳為0.04%至2.0%之重量百分比濃度來存在。
C1-C4烷醇可以0.5%至15.0%，更佳為1.0%至10.0%，最佳為3.0%至7.0%，又更佳為2.0%至6.0%之重量百分比濃度來存在。其較佳選自於乙醇、丙醇、或異丙醇，而最佳為乙醇。
藥物組成物、醫療器械和化妝品都可以按照常規技術來製備，其可包含可接受的賦形劑、佐劑及/或載體，並且還可以在該組合中包含一種以上具有互補的，或是在任何情況下具有有益活性之活性成分。
可以與本發明之標的組成物結合使用之活性劑，包括但不限於，增濕劑(moisturizing agent)、潤滑劑、抗氧化劑、以及維生素；可以使用之賦形劑包括但不限於，較佳為丙二醇之保濕劑、流變添加劑、乳化劑、軟化劑、防腐劑、例如卵磷脂微脂體囊胞(liposome vesicle)之滲透促進劑(penetration enhancer)；天然的、合成的以及半合成聚合物與共聚物、矽酮衍生物、具有增稠(texturizing)與柔焦效果之粉末與填料。
較佳之的丙二醇保濕劑，可以1%至50%，更佳為2%至30%，最佳為5%至20%之重量百分比濃度來存在。
較佳之合成與半合成聚合物係為被稱為卡波姆(Carbomer)之高分子量的丙烯酸之合成聚合物。卡波姆這個術語係指丙烯酸與聚烯基聚醚交聯之均聚物。卡波姆具有吸附、保持水分、並具有可膨脹到原體積之很多倍的能力；其係有助於將不可溶固體散布或懸浮於液體中。其也可以用於維持乳化狀態，而使其不會分離成油與溶液成分。卡波姆通常是用來控制化妝品與個人護理產品之稠度和流動性。
卡波姆可以0.1%至2%，更佳為0.25%至1.5%，最佳為0.5%至1%之重量百分比濃度來存在。
依據本發明之組成物的範例包括：用於局部施用之乳霜、凝膠、軟膏、溶液、乳液、懸浮液。
本發明之藥學組成物及其用途，將透過以下之實施例而更充分加以描述。然而，應當要注意的是，這些實施例僅是用於例示說明，而非侷限本發明。
以下列重量百分比(%)之組成物來製備凝膠形式之配方：
a)將下列成分溶解在純水中：丙二醇12%(重量百分比)-對羥基苯甲酸甲酯鈉0.26%-對羥基苯甲酸丙酯鈉0.03%-乙二胺四乙酸二鈉0.10%-卡波姆0.75%(重量百分比)。
b)將下列成分溶解在乙醇5%中(重量百分比)：維生素E乙酸酯0.02%-卵磷脂0.85%-膽固醇0.01%。
c)將a)與b)分別加熱至60℃並加以結合，用適當渦輪攪拌器(turbo mixer)來均質化；將該化合物冷卻至40℃，並將蛇麻母酊劑(重量百分比)1%於溫和攪拌下加入；將玻尿酸鈉0.05%在總純水量之一部分中預混合，形成均質凝膠，並在攪拌下添加至該化合物中。
d)將咪唑啶基脲0.20%與氫氧化鈉0.12%，在總純水量之一部分中預混合，並在攪拌下依序加入並將該化合物充分混合，直到獲得均勻的凝膠。
為了藉由一種生物方法來評估實施例1之組成物的協同作用之活性，製備下述組成物：
以下列重量百分比(%)之組成物來製備凝膠形式之配方：
以下列重量百分比(%)之組成物來製備凝膠形式之配方：
以下列重量百分比(%)之組成物來製備凝膠形式之配方：
以下列重量百分比(%)之組成物來製備凝膠形式之配方：
相較於實施例1的組成物，比較組成物2缺少啤酒花萃取物與玻尿酸兩者；比較組成物3缺少玻尿酸；比較組成物4缺少啤酒花萃取物；而最後比較組成物5則缺少乙醇。依據本實施例1的組成物，是唯一同時含有啤酒花萃取物、玻尿酸、以及乙醇者。
為了測試實施例1之組成物相對於實施例2之比較組成物2-5的不同抗氧化活性，此等係在不同濃度下(0.500-0.016毫克/毫升)下，在角質細胞於具有與不具有測試樣品下，暴露於紫外光A(UVA)之後，針對活性氧物種(ROS)進行測試，並透過中性紅攝取(NRU)試驗，來評估在歷經UVA逆境之後的細胞存活率：細胞存活分析使用具有與不具有測試樣品之以單層培養的方式培養的人類角質細胞。
人類初代角質細胞係來自於倫理委員會所批准之預先計劃的例行外科手術由來的小兒包皮。該表皮層係藉由靜置培養三並以胰蛋白酶來處理，自真皮層分離而產生單細胞懸浮液。
角質細胞係被培養於富含10%之胎牛血清(體積百分比)以及特定營養之經杜百可修改之伊格爾培養基(Dulbecco’s Modified Eagle’s Medium)與’哈姆F12培養基(Ham's F12 Medium)(3：1)中。
這些細胞係在培養皿中增殖，直到形成單層細胞為止。在這項研究中係將細胞接種至96孔盤內，並在24小時內達到半滿盤(semi-confluency)之狀態(30000細胞/孔)。一旦達到60-70%滿盤的狀態，便加入具有測試樣品的標準量稀釋液的新鮮培養基。未經處理的細胞係被用來作為陰性對照組。在這個階段，細胞培養係以測試化合物與對照組之不同稀釋液來進行處理，以得到
0.5到0.016毫克/毫升之最終濃度範圍。每種稀釋液都進行三重複試驗。該等產物係被溶解於培養基中。分開加入0.15毫克/毫升之維生素C以作為陽性對照組。部分的細胞係以NRU分析來檢測此等之存活性。然後將剩餘的細胞暴露於4'(1焦耳/平方厘米)、8'(2焦耳/平方厘米)與12'(3焦耳/平方厘米)下。在曝光期間結束時，檢測細胞上清液中之活性氧的形成。在以UVA照射之後以及並未照射紫外線的狀態，確認細胞之存活率。
在將細胞暴露於測試樣品之後，將細胞培養液除去，並將細胞以PBS進行洗滌。將二氯螢光黃之乙酸酯溶液(DCA)加入至各孔中。DCA會與培養基中之自由基反應以誘生螢光衍生物，而螢光計讀數可獲得與細胞中之活性氧含量有關的定量數據。
在適當的培養之後，DCA溶液將會被移除，然後細胞將會被暴露於不同時間之UVA照射下，並且如所描述的隨後很快地以螢光計來讀取讀數(Toxicol.Letters 1997-93：47-54)。
NRU分析，係以細胞攝取並結合屬於一種重要色素的中性紅(NR)的能力為基礎。NRU為一種弱陽離子性染料，其透過非離子性擴散機制而穿透細胞膜，並且累積在溶體內之基質的陰離子部位。細胞和溶體膜的改變會造成溶體脆弱，及細胞中漸進而不可逆轉之變化。這些由外來化合物誘發之變化，決定NR攝取以及其與溶體之連結性的降低。這種方法可以用來區分存活、受損、或是死亡的細胞。細胞係以具有標準量濃度
之產品以及中性紅溶液(NR)進行培養。如果細胞膜被破壞，則其會將染料釋放至培養基中。
在進行培養之後，將該培養基以新鮮培養基+NR培養基來替換，並將細胞於37℃下培養4個小時。然後將該細胞洗滌多次，以去除過多之染料廢液，並以比色計讀取。
將所得到的結果以存活率來表示：細胞存活率%=經處理細胞的OD值×100/未經處理的對照細胞之OD值。
總結在表I中之結果，顯示在次毒性測試(sub-toxic test)濃度下(0.016毫克/毫升與0.031毫克/毫升)，研究產品可減少在UVA逆境處理(短時間曝光)之後所產生的ROS。
選擇引用<10%之活性氧抑制效果作為臨界值，顯示具有測試產品之抗活性氧作用優於其他不具備蛇麻、玻尿酸及/或乙醇之配方，甚至優於濃度高達測試產品之10和5倍的對照組(0.15毫克/毫升之維生素C)。
為了測試本案實施例1之組成物相對於實施例2的比較組成物2-5的不同膠原蛋白再生活性，此等係藉由接受以該測試組成物處理的人類皮膚纖維母細胞之膠原蛋白合成的活體外評估而進行試驗。該膠原蛋白的重新合成(ex-novo synthesis)係藉由比色分析來進行測量。
測試產品係以細胞培養基稀釋，以達到被選定以進行測試之最終濃度。該等產物係在20%、10%、5%、2.50%、1.25%、0.63以及0.31%(重量/體積)下，用於初步的細胞毒性測試。根據毒性數據(IC50=6.79%，不具細胞毒性)，選定3種不同之不具細胞毒性的濃度來繼續進行測試。所選定以進行有效性測試之濃度為2.50%、1.25%與0.63%(重量/體積)。將細胞暴露於測試產品延長至24小時與48小時。在每項實驗時間結束時，量測新合成之細胞外基質元素。
膠原蛋白之合成的測定是透過定量染料結合法來進行。在該分析中所使用的顯色劑是天狼星紅(直接紅80)。這些基團會與膠原蛋白之鹼性胺基酸的側鏈基團反應。在測定條件下，該染料對於膠原蛋白之專一性親和力，是由於經延長的染料分子，與具有完整三股螺旋構造的天然膠原蛋白所具有之長鏈剛性結構平行對齊(在膠原蛋白變性時則染料親和性大幅減低)。膠原蛋白的濃度(於20微升培養液中之微克數)，係藉由以已知而
遞增之膠原蛋白濃度所得到的標準曲線上，採用數據內插法而加以計算。該產品測試在所有測試濃度中，於所有的監測實驗時間內，都在增加膠原蛋白合成的速度上，得到比起未經處理的細胞、以及不具備蛇麻、玻尿酸及/或乙醇之其他配方更為顯著之有效結果(以0.63%之研究產品處理48小時的細胞中之膠原蛋白含量，比起未經處理的細胞中的膠原蛋白含量，兩者之間的變化並不顯著)。該增加量係與劑量相關。將該結果總結於表Ⅱ中。
Claims (14)
- 一種組成物，其包含：a)蛇麻(Humulus lupulus)萃取物，b)玻尿酸或是其藥學上可接受的鹽類或酯類，c)C1-C4烷醇，其中該玻尿酸或是其藥學上可接受的鹽類或酯類，係以重量百分比濃度0.04%至2.0%而存在，並且其中，C1-C4烷醇係以重量百分比濃度0.5%至15%而存在。
- 如請求項1之組成物，其中該萃取物為液態、半固態或固態萃取物。
- 如請求項1之組成物，其中該液態萃取物為母酊劑(mother tincture)。
- 如請求項3之組成物，其中該萃取物含量佔該總組成物重量的0.1至15%，較佳為0.2至5%。
- 如請求項4之組成物，其中該含量為0.5至2.5%。
- 如請求項1之組成物，其中該藥學上可接受的鹽類係選自於鈉鹽、鉀鹽、鈣鹽或是具有天然胺基酸之鹽類。
- 如請求項1之組成物，其中該藥學上可接受的酯類係選自於玻尿酸抗壞血酸酯、玻尿酸棕櫚醯酯、玻尿酸芐酯、丁醯鈉玻尿酸酯(sodium butyroyl hyaluronate)、丁醯/甲醯鈉玻尿酸酯(sodium butyroyl/formoyl hyaluronate)。
- 如請求項1之組成物，其中該C1-C4烷醇為乙醇。
- 如請求項1之組成物，其中該C1-C4烷醇的含量佔總組成物重量的1至10%。
- 如請求項9之組成物，其中該含量為3至7%。
- 如請求項10之組成物，其中該含量為2.0至6.0%。
- 如請求項1至11中任一項之組成物，其進一步包含一種以上之以下成分：增濕劑(moisturizing agent)、潤滑劑、抗氧化劑、例如微脂體囊胞(liposome vesicle)與維生素之滲透促進劑(penetration enhancer)；保濕劑、流變添加劑、乳化劑、軟化劑、防腐劑；天然的、合成的或是半合成的聚合物與共聚物、矽酮衍生物、具有增稠(texturizing)與柔焦效果之粉末與填料。
- 如請求項1至12中任一項之組成物，其係用於處理與預防皮膚老化及/或皺紋。
- 如請求項13之用途之組成物，其中接受此等處理者為人類。
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| EP13179245.9A EP2835130A1 (en) | 2013-08-05 | 2013-08-05 | Composition for skin anti-ageing treatment |
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| JP6647832B2 (ja) * | 2015-03-13 | 2020-02-14 | サントリーホールディングス株式会社 | ノンアルコールのビールテイスト飲料 |
| US9993578B1 (en) * | 2017-01-12 | 2018-06-12 | Lorstan Pharmaceutical, LLC | Silicone oil-in-water composition useful as an injectable filler and as a scaffold for collagen growth |
| CN109078220A (zh) * | 2018-08-27 | 2018-12-25 | 白晋 | 一种包含自体胶原蛋白的复合制剂及其应用 |
| CN110467689A (zh) * | 2019-09-09 | 2019-11-19 | 山东众山生物科技有限公司 | 一种透明质酸衍生物及其制备方法 |
| WO2025219934A1 (en) * | 2024-04-18 | 2025-10-23 | The Wave Innovation Group S.R.L. | Composition based on hyaluronic acid, epigallocatechin-3-o- gallate and/or xanthohumol |
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| JP3045590B2 (ja) * | 1991-12-24 | 2000-05-29 | 鐘紡株式会社 | 養毛化粧料 |
| RU2078561C1 (ru) * | 1994-04-28 | 1997-05-10 | Стекольников Леонид Ильич | Косметическое средство, предотвращающее старение кожи |
| JP3634112B2 (ja) * | 1997-03-31 | 2005-03-30 | 株式会社資生堂 | 皮膚外用剤 |
| JP3504590B2 (ja) * | 2000-06-28 | 2004-03-08 | 株式会社ノエビア | 皮膚外用剤 |
| US20030039747A1 (en) * | 2001-08-27 | 2003-02-27 | Optinel Systems,Inc. | Method of enhancing waveguide photosensitivity and waveguide having enhanced photosensitivity |
| JP2003261435A (ja) * | 2002-03-11 | 2003-09-16 | Ichimaru Pharcos Co Ltd | エネルギー変性剤 |
| JP2004035440A (ja) * | 2002-07-02 | 2004-02-05 | Ichimaru Pharcos Co Ltd | くすみ抑制剤及び肌質改善用皮膚外用剤 |
| ITMI20060122A1 (it) | 2006-01-25 | 2007-07-26 | Polichem Sa | Composizioni per uso vaginale |
| JP2008050311A (ja) * | 2006-08-25 | 2008-03-06 | Kowa Co | 使用感の良い乳化組成物 |
| DE102008014289A1 (de) * | 2008-03-11 | 2009-09-17 | Coty Prestige Lancaster Group Gmbh | Kosmetikum mit Anti-Alterungswirkung |
| KR20140129081A (ko) * | 2012-02-15 | 2014-11-06 | Jfe 죠코 가부시키가이샤 | 연질화용 강 및 이 강을 소재로 하는 연질화 부품 |
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- 2014-08-04 WO PCT/EP2014/066723 patent/WO2015018792A1/en not_active Ceased
- 2014-08-04 EP EP14747043.9A patent/EP3030219A1/en not_active Withdrawn
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| WO2015018792A1 (en) | 2015-02-12 |
| CN105555250A (zh) | 2016-05-04 |
| US20160175241A1 (en) | 2016-06-23 |
| EP2835130A1 (en) | 2015-02-11 |
| IL243759A0 (en) | 2016-04-21 |
| UY35695A (es) | 2014-10-31 |
| WO2015018791A1 (en) | 2015-02-12 |
| AR097216A1 (es) | 2016-02-24 |
| EP3030219A1 (en) | 2016-06-15 |
| AU2014304620A1 (en) | 2016-02-25 |
| CA2919771A1 (en) | 2015-02-12 |
| JP2016527292A (ja) | 2016-09-08 |
| MX2016001686A (es) | 2016-11-30 |
| HK1220138A1 (zh) | 2017-04-28 |
| BR112016002580A2 (pt) | 2017-08-01 |
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