TWI610678B - 柑橘多酚於促進傷口癒合之用途及其組成物 - Google Patents
柑橘多酚於促進傷口癒合之用途及其組成物 Download PDFInfo
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- TWI610678B TWI610678B TW104118574A TW104118574A TWI610678B TW I610678 B TWI610678 B TW I610678B TW 104118574 A TW104118574 A TW 104118574A TW 104118574 A TW104118574 A TW 104118574A TW I610678 B TWI610678 B TW I610678B
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Abstract
本發明提供一種用於促進傷口癒合之組成物,包含有效量之柑橘多酚。本發明亦提供一種柑橘多酚用於製備促進傷口癒合及促進纖維母細胞增生及/或遷移之組成物的用途。
Description
本發明係關於一種柑橘多酚之用途,尤其係關於一種柑橘多酚用於製備促進傷口癒合之組成物之用途。
傷口癒合係複雜的動態過程,理想的傷口癒合係回到正常的組織結構、功能及外觀。一般傷口若經過適當處理,大多可在1至2週癒合;但若處理不當則可能導致傷口癒合緩慢並發生潰瘍,輕者造成傷口永久性疤痕,重者則嚴重到傷口演變成蜂窩性組織炎,需透過患處傷口清創手術、植皮或截肢以保住性命。
在各式傷口中,口腔潰瘍為成年人的常見口腔問題。潰瘍為多數口腔疾患的症狀之一,並且經常對患者造成強烈的痛感以及不適。口腔潰瘍引起之原因往往為物理性創傷、缺乏維生素、細菌感染等。一般而言,小面積的潰瘍會在少於一週的時間內復原;但當潰瘍面積之直徑大於1公分時,其癒合時間將長達數月。
傷口或潰瘍的種類、大小,以及患者的營養狀況、年紀、其他系統疾病、使用的藥物等許多因素,都會影響其
癒合的過程及時間。先前技術中有關潰瘍的處理大多為投予營養素之支持療法(supportive play chotherapy),或為局部施用類固醇或有殺菌能力之藥劑,以減少潰瘍面積、避免再次感染並縮短傷口癒合時間。
然而,對於病毒或細菌引起之潰瘍以及患有低免疫力疾病之患者並不適合使用類固醇消炎藥;而具有殺菌能力之藥劑,例如常用的含酒精之外用液劑或優碘,則會對傷口癒合時需要的纖維母細胞造成破壞和傷害。
纖維母細胞在傷口癒合中扮演十分重要的角色。Li YC等人在“Pearl extract enhances the migratory ability of fibroblasts in a wound healing model”(Pharm Biol;2013 51:289-297)中指出,當感測到傷口出現時,纖維母細胞會轉變成活化態之多角形表現型;Khovidhunkit S.O.等人在“In vitro study of the effects of plaunotol on oral cell proliferation and wound healing”(J Asian Nat Prod Res;2011 13:149-159)中指出,當傷口癒合時,纖維母細胞將會增生並遷移至傷口位置以修復傷口;Lamme E.N.等人在“Higher numbers of autologous fibroblasts in an artificial dermal substitute improve tissue regeneration and modulate scar tissue formation,”(J Pathol 2000;1900:595-603)中亦指出,纖維母細胞數量的增加改善了試驗模型中傷口癒合的情形。
目前已知植物中所萃取出的多種多酚類化合物在生理上具有不同的功效,舉例而言,Ferruelo等人在“Effects of
resveratrol and other wine polyphenols on the proliferation,apoptosis and androgen receptor expression in LNCaP cells”中提出白藜蘆醇(resveratrol)和其他紅酒多酚對前列腺癌細胞LNCaP具有抑制其增生的能力(Actas Urológicas Españolas(English Edition)2014;38:397-404);Schoene等人在“Water-soluble polymeric polyphenols from cinnamon inhibit proliferation and alter cell cycle distribution patterns of hematologic tumor cell lines”中提出萃取自肉桂的聚合多酚類對血液腫瘤細胞株有抑制其生長的功效(Cancer Letters 2005;230:134-140);Leifert等人在“Grape seed and red wine polyphenol extracts inhibit cellular cholesterol uptake,cell proliferation,and 5-lipoxygenase activity”中提出葡萄和紅酒多酚萃取物抑制細胞增生(Nutrition Research 2008;28:842-850)。
而Chen等人在“Effects of the vegetable polyphenols epigallocatechin-3-gallate,luteolin,apigenin,myricetin,quercetin,and cyanidin in primary cultures of human retinal pigment epithelial cells”中則進一步指出植物多酚,如表沒食子兒茶素-3-沒食子酸酯(epigallocatechin-3-gallate)、葉黃酮(luteolin)、芹菜素(apigenin)、楊梅黃酮(myricetin)、槲皮素(quercetin)和矢車菊素(cyanidin)會抑制視網膜色素上皮細胞(Molecular Vision 2014;20:242-258);亦有研究指出表沒食子兒茶素-3-沒食子酸酯抑制血管平滑肌細胞的增生(Z.Shu,M.Yu,G.Zeng,X.Zhang,L.Wu,X.Tan.2014.
Epigallocatechin-3-gallate inhibits proliferation of human aorticsmooth muscle cells via up-regulating expression of mitofusin.European Journal of Cell Biology 93:137-144;P.L.Liu,J.T.Liu,H.F.Kuo,I.W.Chong,and C.C.Hsieh.Epigallocatechin Gallate Attenuates Proliferation and Oxidative Stress in Human Vascular Smooth Muscles Cells Induced by Interleukin-1β via Heme Oxygenase-1.2014.Mediators of Inflammation Article ID 523684,http://dx.doi.org/10.1155/2014/523684)。
然而,習知口腔用組成物(例如漱口水)之添加物多為茶、竹多酚,其功能僅為殺死牙菌斑病並預防齲齒,沒有先前技術揭示可有效促進纖維母細胞增生的植物多酚類化合物。有鑑於目前對傷口或潰瘍癒合的治療方式中大多使用會導致其他副作用化學物質,可能導致患者不適或延宕癒合時間之風險,故亟需可以有效促進傷口癒合而又不致其他不欲結果之解決方法。
有鑑於以上所述之問題,本發明提供一種柑橘多酚用於製備促進傷口癒合之組成物之用途,其中,該組成物包含有效量之柑橘多酚和醫藥上可接受之載劑。
根據本發明之具體實施例,該柑橘多酚包括飛燕草素(delphinidin)、天竺葵苷素(pelargonidin)、芍藥素(peonidin)、錦葵色素(malvidin)、矢車菊素(cyanidin)、柚皮芸香苷(narirutin)、柚皮苷(naringin)、橙皮苷(hesperidin)及
新橙皮苷(neohesperidin)。
根據本發明提供之具體實施例,該傷口係皮膚外傷、燒燙傷、皮膚潰瘍或口腔潰瘍。根據本發明之一具體實施例,該組成物係用以促進纖維母細胞增生及/或遷移,從而促進傷口癒合。
根據本發明之具體實施例,以該組成物之總重計,該柑橘多酚之含量為大於0wt%至小於1wt%。於一具體實施例中,該柑橘多酚之含量係大於0wt%至小於等於0.1wt%。於一具體實施例中,該柑橘多酚之含量係0.01wt%。
又,根據本發明之一態樣,本發明提供一種柑橘多酚用於製備促進纖維母細胞增生及/或遷移之組成物之用途。
根據本發明之另一態樣,本發明提供一種用於促進傷口癒合之組成物,包含有效量之柑橘多酚和醫藥上可接受之載劑。
根據本發明之具體實施例,該組成物係用於口腔之組成物。根據本發明之另一具體實施例,該組成物係呈選自下列所組成群組之其中一者的劑型:漱口水、牙粉、牙膏、牙膠、牙周膠、可嚼片、薄膜、口含片、口腔凝膠、口腔錠劑和泡沫劑。
根據本發明之具體實施例,該醫藥上可接受之載劑係選自下列所組成群組之至少一者:發泡劑、崩解劑、賦形劑、黏度調節劑、稀釋劑、介面活性劑、pH調整劑、磨料、濕潤劑、口感劑、甜味劑、香料、著色劑、防腐劑、安定劑及抗菌劑。
第1A圖係經不同濃度柑橘多酚處理4小時後之Hs68細胞之光學顯微鏡圖;第1B圖係經不同濃度柑橘多酚處理3天後之Hs68細胞之光學顯微鏡圖;第1C圖係經不同濃度柑橘多酚處理6天後之Hs68細胞之光學顯微鏡圖,其中,該光學顯微鏡圖之比例尺為100μm;第2A圖係在含不同濃度柑橘多酚之培養基中Hs68細胞之MTT試驗結果;第2B圖係在含不同濃度柑橘多酚之培養基中Hs68細胞之乳酸去氫酶試驗(Lactic dehydrogenase(LDH)assay)結果,*p<0.01表示具有顯著性差異;第3A圖顯示在控制組培養基(不含柑橘多酚)中進行刮痕試驗16小時內之Hs68細胞之動態進程;第3B圖顯示在含0.1%柑橘多酚之培養基中進行刮痕試驗16小時內之Hs68細胞之動態進程;第3C圖顯示在含0.01%柑橘多酚之培養基中進行刮痕試驗16小時內之Hs68細胞之動態進程;第3D圖顯示在含不同濃度柑橘多酚之培養基中進行刮痕試驗,16小時後遷移至刮痕位置之Hs68細胞之平均數量,其中,第3A至3C圖之比例尺為100μm,**p<0.01表示具有顯著性差異;以及第4A至4C圖係分別在不含柑橘多酚、含0.1%柑橘多酚或含0.01%柑橘多酚之培養基中進行刮痕試驗3天內之Hs68細胞之光學顯微鏡圖,其中,該光學顯微鏡圖之比例尺為100μm。
以下係藉由特定的具體實施例說明本發明之實施方式,熟習本技術領域者可由本說明書所揭示之內容了解本發明之其他優點及功效。本發明亦可透過不同之具體制定或施用情況而實現,此等指示之細節可依據不違背創作精神之各種修飾及改變中之不同觀點及應用。
須注意的是,如本說明書使用,除非明確且不含糊地限定於一個指示物,否則單數形式之「一」及「該」包括複數指示物。除非上下文另有明確指明,否則術語「或」係與術語「及/或」互換使用。
本發明提供一種柑橘多酚用於製備促進傷口癒合之組成物之用途。根據本發明之具體實施例,該傷口係皮膚外傷、燒燙傷、皮膚潰瘍或口腔潰瘍。
本文中所使用之術語「傷口」係指因物理性或化學性外力導致身體組織結構或器官遭受破壞。更具體而言,該身體組織結構或器官係指皮膚或口腔黏膜組織。一般而言,依照癒合時間,傷口可分為急性傷口與慢性傷口,而所謂慢性傷口,意即任何傷口未依預期時間癒合、或停留在某一個癒合過程過長,例如超過4至6週以上。而本文中所使用之術語「口腔潰瘍」係指口腔黏膜內壁或者舌表面上皮組織遭受破壞產生傷口,該傷口未即時癒合而進一步變為潰爛點。
本發明之組成物中所含之柑橘多酚係一種多酚類混合物,其可使用本技術領域中已知之萃取方法自以柑橘屬
為主之水果中獲得。根據本發明之具體實施例,柑橘多酚包含一或多種活性物質,該些活性物質包括,但不限於:飛燕草素(delphinidin)、天竺葵苷素(pelargonidin)、芍藥素(peonidin)、錦葵色素(malvidin)、矢車菊素(cyanidin)、柚皮芸香苷(narirutin)、柚皮苷(naringin)、橙皮苷(hesperidin)及新橙皮苷(neohesperidin)。較佳地,本發明所使用之柑橘多酚係飛燕草素、天竺葵苷素、芍藥素、錦葵色素、矢車菊素、柚皮芸香苷、柚皮苷、橙皮苷及新橙皮苷的混合物。
根據本發明之具體實施例,該柑橘多酚佔該組成物總重量之大於0wt%至小於1wt%。於另一具體實施例,該柑橘多酚佔該組成物總重量之大於0wt%至小於等於0.1wt%。於另一具體實施例,更佳地,該柑橘多酚佔該組成物總重量之0.01wt%。
又,根據本發明所提供之具體實施例,該組成物除了包含有效量之柑橘多酚外,可進一步包含一或多種醫藥上可接受之載劑。本文中所使用之術語「醫藥上可接受之載劑」係指一般醫藥上可用於製備醫藥組合物之載劑。該醫藥上可接受之載劑之實例包括,但不限於:發泡劑、崩解劑、賦形劑、黏度調節劑、稀釋劑、介面活性劑、pH調整劑、磨料、濕潤劑、口感劑、甜味劑、香料、著色劑、防腐劑、安定劑、抗菌劑或類似試劑。
根據本發明之具體實施例,該組成物可呈液態、半固態、固態或噴霧劑型。較佳地,該組成物係呈粉劑、顆粒劑、液劑、乳劑、霜劑、油膏、凝膠、貼布、噴霧劑、微
乳液或類似劑型。
可用於提供本發明之適當賦形劑及其他材料係本領域具有通常知識者所熟知,且取決於所欲之組成物劑型或所欲施用該組成物之組織。一般而言,典型的賦形劑包括,但不限於:用以形成液態劑型之水、丙酮、乙醇、乙二醇、丙二醇、丁-1,3-二醇、肉豆蔻酸異丙酯、棕櫚酸異丙酯、礦物油或其混合物;用於形成貼布或薄膜等固態劑型之高分子薄膜(諸如聚己內酯薄膜)或高分子塊材(諸如發泡海綿);用於形成固態或膠態劑型之高分子水膠(諸如甲殼素水膠、膠原蛋白水膠及玻尿酸水膠)、高分子微粒或微脂粒、吡咯烷酮類或其混合物。
根據本發明之又一具體實施例,該組成物係用於口腔之組成物。根據本發明之具體實施例,該用於口腔之組成物可以是漱口水、牙粉、牙膏、牙膠(dental gel)、牙周膠(periodontal gel)、可嚼片、薄膜、口含片、口腔凝膠、口腔錠劑、泡沫劑或類似形式調配。舉例而言,當本發明之組成物係以漱口水形式調配時,該組成物可進一步包含習知漱口水中之可口服物質,諸如抗菌劑、食用色素及食用薄荷腦。根據本發明之具體實施例,該抗菌劑包括,但不限於:醫藥上可接受之胍類和季銨鹽類消毒劑,諸如雙氯苯雙胍己烷(chlorhexidine);異噻唑啉酮類化合物;或含氯有機化合物,如三氯生。於另一具體實施例中,該組成物可額外添加其他非多酚類組成物之活性成分,該活性成分包括,但不限於:胺基酸、蛋白質、胜肽、核苷酸、營養
製劑、類固醇、鎮痛劑、消炎劑、抗病毒劑、止血劑、抗過敏劑或類似活性物質。
視欲處理之組織而定,本發明之醫藥組成物中可額外添加成分,例如:可使用滲透來協助將活性成分傳送至組織。適當之滲透增強劑包括,但不限於:丙酮;各種醇類例如:乙醇、丙二醇、四氫呋喃醇(tetrahydrofuryl alcohol);烷基亞碸類例如:二甲亞碸;二甲基乙醯胺;二甲基甲醯胺;聚乙二醇;吡咯烷酮類例如聚乙烯吡咯烷酮;尿素;及多種水溶性或水不溶性糖酯類,例如山梨醇酯80(Tween 80)等。
另一方面,本發明提供一種用於促進受試者傷口癒合之方法,包括施用包含有效量之柑橘多酚之組成物於該受試者。根據本發明之具體實施例,本發明之組成物係施用於傷口處,並且在施用後,該傷口位置周圍之纖維母細胞會產生遷移和/或增生的情形,該纖維母細胞係自傷口位置之周圍逐漸向傷口中心遷移和/或增生,進而促使傷口癒合。
以下係藉由特定之具體實施例進一步說明本發明之特點的功效,但非用於限制本發明之範疇。
人類纖維母細胞Hs68(BCRC編號為60038)係根據Lou PJ等人(Biomaterials 2010;31:1568-1577)及Chung YC等人
(Biomaterials 2011;32:4471-4480)所報導之方法培養。於95%空氣/5% CO2及37℃的環境中,將Hs68細胞培養於含有10%胎牛血清(FBS)(Biological Industries,Israel)的DMEM培養基。於3至5天內使細胞達到聚滿狀態(confluence),並以磷酸鹽緩衝液(PBS)洗滌,接著於37℃以0.05%胰蛋白酶(trypsin)處理5分鐘,使細胞脫離,並使脫離之細胞離心沉澱(spin down)。隨後,以培養基重新懸浮該細胞,然後以大約10000顆細胞/cm2的密度將細胞種於24孔盤(TCPS,Coring)中。四小時後,當細胞皆貼附於孔盤時,將培養基更換成含有10% FBS及分別含有0%、0.1%、0.01%或1%柑橘多酚(購自Fytexia,France)的DMEM培養基,並於每日更換新鮮培養基。
以Lieca DMI600倒立相位差顯微鏡觀察經柑橘多酚培養之Hs68細胞之細胞型態。
請參見第1A至1C圖,第1A至1C圖係經不同濃度柑橘多酚分別處理4小時、3天和6天後之Hs68細胞之細胞型態。如第1B圖所示,經0.01或0.1wt%柑橘多酚培養3天後,可觀察到Hs68細胞有增生現象,且細胞外觀呈現扁平的多角型,顯示與0.01或0.1wt%柑橘多酚培養後,Hs68細胞數量有增加的情形;反之,經1wt%柑橘多酚培養之Hs68細胞則在實驗時間中皆未觀察到增生的情形。又如第1C圖所示,經0.01和0.1wt%柑橘多酚培養6天後之Hs68
細胞逐漸達到聚滿狀態。
此外,從第1A至1C圖中可發現,在0.01wt%柑橘多酚培養中,Hs68細胞大多呈現多角形(活化態),逐漸達聚滿狀態後,轉變為紡錘狀纖維母細胞表現型(非活化態)。
Hs68細胞存活性係透過細胞還原3-(4,5-二甲基噻唑-2基)-2,5-溴化二苯基四唑(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT),Sigma)的能力來評估。由於活細胞中的粒線體去氫酶可選擇性地剪切四唑環,因而產生藍/紫色的甲臢(formazan)結晶,故MTT還原成甲臢之程度可反映出細胞的代謝作用。
為了進行MTT試驗,於測定前將原DMEM培養基移除,並以0.2ml之MTT(5mg/ml,溶於PBS)於37℃培養細胞三小時。培養後,吸取培養基並使用二甲基亞碸(溶於PBS)處理,搖晃15分鐘使甲臢反應產物溶解。使用ELIAS盤讀取儀(M2e,Molecular Devices)偵測甲臢溶液於570nm之光密度(optical density)。
MTT試驗結果如第2A圖所示。當培養六天時,在含0.01wt%柑橘多酚培養基中的Hs68細胞的MTT還原活性顯著高於在不含柑橘多酚培養基中者。此結果顯示0.01wt%柑橘多酚最適於Hs68細胞增生。
利用LDH試驗評估柑橘多酚之細胞毒性。首先,將Hs68細胞依實施例1所述之方式培養。當與柑橘多酚分別培養4小時、3天及6天後,收集100μl/孔之上清液並置入新的96孔盤,接著將100μl乳酸去氫酶(LDH)加入各孔,於37℃培養30分鐘,然後加入50μl之1N HCl。使用ELIAS盤讀取儀(M2e,Molecular Devices)偵測於490nm及630nm之吸光度。
LDH試驗結果如第2B圖所示。經0.01wt%及0.1wt%柑橘多酚培養之Hs68細胞釋放LDH之程度皆小於未經柑橘多酚培養者,且經柑橘多酚培養六天時,可觀察到顯著差異。此結果與實施例2之結果一致,亦即,高濃度(1wt%)柑橘多酚會抑制Hs68細胞之增生,另一方面,0.01wt%及0.1wt%之柑橘多酚可使細胞存活且不抑制細胞增生。
綜合第2A和2B圖之結果可知,本發明所使用之特定濃度的柑橘多酚具有誘導Hs68細胞生長之能力,並且對Hs68細胞不具有毒性。
已有許多研究指出,纖維母細胞可在短時間內增生並遷移至傷口處。纖維母細胞之遷移能力係利用刮痕試驗(scratch assay)評估。為進行刮痕試驗,將Hs68細胞培養於含10% FBS之DMEM培養基中直至聚滿狀態。為製造矩形刮痕,利用吸管尖(pipette tip)輕刮單層細胞,接著移除培養基及脫離之細胞。使用PBS洗滌經刮除之孔兩次,並
加入含有或不含柑橘多酚之新鮮培養基。將細胞培養16小時(短時間)或3天(長時間)。隨後,利用倒立相位差曠時攝影顯微系統(Liesa DMI600,Germany)測定細胞遷移能力。結果如第3A至4C圖所示。
第3A至3C圖分別顯示在不含柑橘多酚、含0.1%柑橘多酚及含0.01%柑橘多酚之培養基中進行刮痕試驗16小時內之Hs68細胞之動態進程;第3D圖顯示在含不同濃度柑橘多酚之培養基中,16小時後遷移至刮痕位置之Hs68細胞之平均數量;第4A至4C圖則分別為在不含柑橘多酚、含0.1%柑橘多酚或含0.01%柑橘多酚之培養基中進行刮痕試驗3天內之Hs68細胞之光學顯微鏡圖。圖中虛線範圍內為刮痕位置,實驗過程中係按時計數在虛線範圍內之細胞,即生長或遷移之纖維母細胞。
請參見第3A及3B圖,可以發現在培養6小時後,在不含柑橘多酚或含0.1%wt柑橘多酚培養基中出現第一個遷移至刮痕位置之Hs68細胞(白色箭頭處)。請參見第3C圖,可以發現在培養4小時後,在含0.01%柑橘多酚培養基中出現第一個遷移至刮痕位置之Hs68細胞(白色箭頭處,三處)。
在Hs68細胞持續遷移的6至16小時內,第3A圖顯示在第16小時時僅有少數細胞遷移至刮痕位置至實驗的觀測終點。此外,與不含柑橘多酚之培養基相比,如第3B和3C圖所示,0.1wt%和0.01wt%柑橘多酚培養基中較多呈現混合型態(多角形和紡錘狀)之Hs68細胞。
請參見第3D圖,在0wt%、0.1wt%和0.01wt%柑橘多酚培養基中刮痕位置之Hs68細胞之數量分別為18±1、21±2和58±2個。由此可見,以柑橘多酚培養之後,刮痕位置中的Hs68細胞數量較多,且在0.01wt%柑橘多酚培養基之細胞數量為0wt%柑橘多酚培養基之三倍。
第4A至4C圖顯示與柑橘多酚培養長時間(3天)之刮痕試驗結果。可以發現,經0.01wt%柑橘多酚培養2天後,Hs68細胞生長至將近全滿,顯示纖維母細胞不僅逐漸遷移至刮痕位置,且其遷移速度也比控制組(不含柑橘多酚)來的快速。由此可見,0.01%柑橘多酚可提供較快的速度來修復傷口。
由本實施例之結果可知,經柑橘多酚,特別是0.01wt%之柑橘多酚處理後,可使Hs68細胞具有較佳之遷移能力,將有助於促進傷口癒合。
所有試驗皆經過六重複測定後,將所得之數據進行單因子變異數分析(analysis of variance,ANOVA)及事後檢定(post hoc)(即鄧肯氏新多變域檢定法(Duncan's test)),檢測各處理組平均值間之差異顯著性。
本發明之一實施例所製備之組成物為局部水凝膠,係用於表皮傷口或潰瘍癒合。根據本發明之實施例,較佳地,
該局部水凝膠之使用劑量可為每日一次、每日兩次、每日三次或視需要使用。又,當施用該局部水凝膠於傷口或潰瘍時,係使該局部水凝膠接觸該傷口或潰瘍位置並停留一段時間。
根據本發明之實施例,該局部水凝膠之製作方法步驟如下,各成分比例如表1所示:(1)先將柑橘多酚以水稀釋配置為所需濃度,獲得溶液A;(2)將聚乙烯吡咯烷酮或其聚合物溶於水,獲得溶液B;(3)將溶液A倒入溶液B中,並充分混合;(4)將步驟(3)之混合溶液於無菌室溫環境靜置一段時間,以獲得含柑橘多酚之局部水凝膠。
本發明之一實施例所製備之組成物為牙膏,係用於緩解口腔中傷口或潰瘍之症狀。根據本發明之實施例,較佳地,該牙膏之使用劑量可為每日一次、每日兩次、每日三
次或視需要使用。
根據本發明之一具體實施例,其製作方法步驟如下,各成分比例如表2所示:(1)先將柑橘多酚以水稀釋配置為所需濃度,得溶液A;(2)將濕潤劑和其他添加物溶於水,獲得混合物B;(3)將溶液A倒入溶液B中,並充分混合;(4)將研磨劑加入步驟(3)之混合溶液後攪拌均勻,以獲得含柑橘多酚之牙膏。
本發明之一實施例所製備之組成物為漱口水,係用於緩解口腔中傷口或潰瘍之症狀。根據本發明之實施例,較佳地,該漱口水之使用劑量可為每日一次、每日兩次、每日三次或視需要使用,每次以適量之漱口水劑於口腔內漱洗並停留一段時間後吐出,該停留時間可為10至60秒、20至60秒、30至60秒,較佳為30至60秒。
根據本發明之一較佳實施例,該漱口水中之各成分比例如表3所示。將各成分混合後攪拌均勻,充分溶解後即得含柑橘多酚之漱口水。
本發明證實添加柑橘多酚於促進傷口癒合之組成物中能夠有效誘導纖維母細胞之增生和遷移並促進傷口癒合,同時縮短傷口癒合的時間。
此外,本發明藉由將柑橘多酚作為習知醫藥組成物(例如口內膏、漱口水、口內添片等)之添加物,無須改變原有醫藥組成物之成分,且不影響該醫藥組成物原有功效,便可生產出具有多重效果之有效促進傷口癒合之組成物。
上述實施方式僅為例示性說明本發明之原理及其功效,而非用於限制本發明。任何熟習此項技藝之人士均可在不悖離本發明之精神及範疇下,對上述實施例進行修飾與變化。因此,本發明之權利保護範圍,應如後述之申請專利範圍所列。
本案圖式均為實驗數據圖式,故無指定代表圖。
Claims (14)
- 一種柑橘多酚用於製備促進傷口癒合之組成物之用途,其中,該組成物包含有效量之柑橘多酚和醫藥上可接受之載劑,其中,該柑橘多酚包括飛燕草素、天竺葵苷素、芍藥素、錦葵色素、矢車菊素、柚皮芸香苷、柚皮苷、橙皮苷及新橙皮苷;以及該柑橘多酚的有效量為大於0wt%至小於1wt%。
- 如申請專利範圍第1項所述之用途,其中,該傷口係皮膚外傷、燒燙傷、皮膚潰瘍或口腔潰瘍。
- 如申請專利範圍第1項所述之用途,其中,該組成物係用以促進纖維母細胞增生及/或遷移,從而促進傷口癒合。
- 如申請專利範圍第1項所述之用途,其中,該柑橘多酚的有效量為大於0wt%至小於等於0.1wt%。
- 如申請專利範圍第4項所述之用途,其中,該柑橘多酚的有效量為0.01wt%。
- 一種柑橘多酚用於製備促進纖維母細胞增生及/或遷移之組成物之用途,其中,該組成物包含有效量之柑橘多酚和醫藥上可接受之載劑,其中,該柑橘多酚包括飛燕草素、天竺葵苷素、芍藥素、錦葵色素、矢車菊素、柚皮芸香苷、柚皮苷、橙皮苷及新橙皮苷;以及該柑橘多酚的有效量為大於0wt%至小於1wt%。
- 如申請專利範圍第6項所述之用途,其中,該柑橘多酚的有效量為大於0wt%至小於等於0.1wt%。
- 如申請專利範圍第7項所述之用途,其中,該柑橘多酚的有效量為0.01wt%。
- 一種用於促進傷口癒合之組成物,包含:有效量之柑橘多酚;以及醫藥上可接受之載劑,其中,該柑橘多酚包括飛燕草素、天竺葵苷素、芍藥素、錦葵色素、矢車菊素、柚皮芸香苷、柚皮苷、橙皮苷和新橙皮苷;以及該該柑橘多酚之含量為大於0wt%至小於1wt%。
- 如申請專利範圍第9項所述之組成物,其中,以該組成物之總重計,該柑橘多酚之含量為大於0wt%至小於等於0.1wt%。
- 如申請專利範圍第10項所述之組成物,其中,以該組成物之總重計,該柑橘多酚之含量為0.01wt%。
- 如申請專利範圍第9項所述之組成物,係用於口腔之組成物。
- 如申請專利範圍第12項所述之組成物,係呈選自下列所組成群組之其中一者的劑型:漱口水、牙粉、牙膏、牙膠、牙周膠、可嚼片、薄膜、口含片、口腔凝膠、口腔錠劑和泡沫劑。
- 如申請專利範圍第9項所述之組成物,其中,該醫藥上可接受之載劑係選自下列所組成群組之至少一者:發泡劑、崩解劑、賦形劑、黏度調節劑、稀釋劑、介面活性劑、pH調整劑、磨料、濕潤劑、口感劑、甜味劑、香料、著色劑、防腐劑、安定劑及抗菌劑。
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