系列異黃酮衍生物之活性評估與微脂粒劑型之穿透研究

Investigation of liposomes as carriers of a series of isoflavone derivatives in permeation and bioactivity evaluations

翁榮敏(Jung-Min Weng)

指導教授 ： 黃耀斌

高雄醫學大學/藥學院/藥學研究所/碩士(2005年)

摘要

中文摘要
有相當多研究報導說明大豆異黃酮有許多生物活性例如：tyrosinase inhibitor、topoisomerase II inhibitor、抗氧化能力、抗癌活性、預防心血管疾病、防護化學性傷害及植物性荷爾蒙(荷爾蒙替代療法)作用等，加上於安全劑量下毒性極低，所以被認為是具有開發價值的醫療成分。因此在本研究中，將以大豆異黃酮為主軸，將研究焦點放在皮膚活性上，以開發新型皮膚保養製劑為目的。
本研究以大豆異黃酮類(soy-isoflavones)中最主要的兩種具活性之異黃酮類成分genistein及daidzein，以此兩種結構為骨架進行系列合成異黃酮之評估，其化學結構屬非固醇類之異環酚類，與17??-estradiol之結構近似，而其中之phenolic ring對於不論是與??-或??-型的雌性素(estrogen)接受體之結合而言均是不可缺少的結構。因此本研究以二十一種合成異黃酮進行系列活性評估研究與劑型-微脂粒研究。首先，對各衍生化合物進行皮膚活性之篩檢，包含酪胺酸酵素抑制活性(tyrosinase inhibition)及抗氧化活性與清除自由基活性分析，結果顯示以合成之IF-2H (編號G)及IsoF-3D (編號R)兼具三項之活性，同時以存在大豆異黃酮中之主成分genistein(編號B)及daidzein(編號D)為對照成分進行物性及皮膚穿透之研究。並選定微脂粒為藥物傳遞系統。
在體外穿透實驗中顯示，分配係數與12小時累積穿透量成正比而且穿透量也與皮內含量成正比，並成功的以微脂粒劑型提昇活性成分G跟R的穿皮效果與皮膚含量。
在體內模式的中，將以天竺鼠為動物模式，觀察活性藥物之微脂粒處方對皮膚的影響。研究結果顯示，紫外線照射會使皮膚的ΔL*值下降，Δa*值上升；使水分散失速率上升；也有脫毛的現象。在投予微脂粒處方評估後，觀察到G跟R微脂粒處方在黑色素還原能力評估中能使皮膚的ΔL*值上升，降低Δa*值，更能顯著的降低水分散失速率，且處方不具刺激性；但其成份效果不盡相同，但以G的效果最為顯著(p<0.05)。
本研究結果顯示，本實驗能初步成功的發展出一新型的保養製劑；包覆活性成分G跟R的微脂粒劑型。

關鍵字

異黃酮 ； 微脂粒

並列摘要

Abstract
In recent years, a lot of studies reported that isoflavones are associated with a number of health benefit, including tyrosinase inhibitor, topoisomerase II inhibitor, antioxidant activity, hormone replacement therapy, cardiovascular function, anticancer, anti-inflammatory, protect photodamages from UV. Besides isoflavones are safe at physiological concentration. So it is considered that worthy to study as economical medical compounds. The present study is focus on isoflavones, and focal point is on skin activities to develop new skin-care agents.
The purpose of this experiment was to synthesis a series of isoflavone derivatives in accordance with the bone structures of genistein and daidzein in order to find new active compounds and evaluates penetration in skin. Their chemical structures are the presence of a phenolic ring which is a prerequisite for binding to the α- or β- estrogen receptor. So this study is to evaluation 21 isoflavone derivatives of bioactive and liposome studies. First their tyrosinase inhibition, antioxidation activity and free radical scavenging activity were performed to evaluate the effect of skin care. According to these investigations, we selected two compounds, IF-2H (G) and IsoF-3D (R) which had higher bioactivity than genistein and daidzein as active compounds. In order to compare simultaneously the penetration of the natural compounds in soy-isoflavones, we used the genistein (B) and daidzein (D) as references to compare the physicochemical properties with selected compounds.
In vitro permeation studies, the partition coefficient and 12h skin accumulation amount are direct proportion; the flux and druds deposition in whole skin are direct proportion；liposomes are suitable carrier systems for topical application of G and R.
In vivo experiment, we will choose guinea pigs as model to evaluation. In our study, UV exposure will decrease ΔL*; increase Δa*; increase TEWL and molt symptom. After topical application of liposome formulation in reduce pigmentation study will increaseΔL*; decrease Δa*; significantly decrease TEWL, and liposome formulation have no skin irritation, especially in G liposome (p<0.05).
By means of in vitro and in vivo experiments, G liposome and R liposome may be successfully employed as topical skin care agent.

並列關鍵字

permeation ； liposome ； isoflavone

參考文獻

陸、參考文獻

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