黃芩之解熱效應及其指標成分Baicalein經固相脂質奈米顆粒化之藥物輸送系統研究

Antipyretic effect of the extract from Scutellaria in vivo study and the SLN formulation design of its biomaker, baicalein, as drug delivery system

林金霖(Chin-Lin Lin)

指導教授 ： 吳寶珠

高雄醫學大學/藥學院/藥學研究所/碩士(2006年)

摘要

黃芩為唇型科植物，自古以來為中國傳統中藥，具有解熱、抗炎的作用。Baicalein為黃芩的主成分，在生物體內扮演著重要的角色，能夠抑制促發炎（pro-inflammatory ）酵素的產生和減少PGE2的產生，以達到解熱的目的。本實驗主要是利用酵母誘導大鼠體溫升高，藉由口服黃芩煎煮液及其主成分baicalein和baicalin，在不同劑量下觀察時間與抑制率的關係，由實驗結果得知，黃芩在低劑量時就可以看出其解熱效果。經由口服及腹腔注射黃芩冷凍乾燥粉末，都無法明顯的經由HPLC偵測出baicalein在血漿中的濃度，證實了baicalein在血漿中的不安定性。所以將baicalein製成SLN的劑型，觀察是否能增加baicalein在血漿中的安定性，選用Gelucire（62/5、48/9、44/14）及glyceryl monostearate當作脂質的部份，配合不同劑量之抗氧化劑vitamin C及vitamin E，評估處方在6天內粒徑平均大小和baicalein的含量，篩選出具有高包埋率的處方為含8 mg vitamin C之Gelucire 62/5，將其製成SLN，以靜脈注射投予，觀察大鼠體內血漿中藥物動力學情形以及腦部組織的分布。由實驗結果得知，將baicalein製成SLN的劑型，可以發現t1/2及MRT都增加1個小時，清除率有顯著減少，血漿中AUC提高，平均血中濃度的波峰比baicalein-solusion高出5倍，使得baicalein能在血漿濃度提高，說明baicalein-SLN有助於延長baicalein在血漿中的時間。HPLC偵測結果發現視丘中具有高濃度的baicalein，證明baicalein能穿透血腦障壁，抵達腦部視丘，以致能夠影響視丘調解體溫的功能，達到解熱的目的。

關鍵字

黃芩 ； 解熱 ； 固相脂質奈米顆粒化

並列摘要

The medicinal plant Scutellaria baicalensis Georgi (Lamiaceae) (SR) has been used widely in traditional Chinese medicine for antipyretic and anti-inflammation. Baicalein is the main ingredient of SR and plays an import role in medicine due to its mechanism of reducing the production of pro-inflammatory enzyme and consequently decreasing the release of PEG2. This study was to estimate the antipyretic effect of baicalin and baicalein with different dose in rats by observing the relationship between time and rate of antipyretic effect. The results was shown that low dose of SR could produce better antipyretic effect than of higher dose. After orally and intravenously administration of freeze-dried powder of SR decoction injected into the rat, the blood concentration of baicalein could not be detected by HPLC. It was confirmed that baicalein was fastly eliminated in blood. The formulation of SLN prepared with Gelucire (62/5, 48/9 and 44/14) and glyceryl monostearate as lipid phase and Vitamin C and Vitamine E as antioxidant to overcome the problem. The formulation was evaluated by measuring the average particle size and the content of baicalein at 6th day. The SLN with the highest entrapment efficiency was composed of Gelucire 62/5 with 8 mg of Vitamin C, and then was intravenously administrated into the rat. The pharmacokinetics and distribution of baicalein in brain tissue were evaluated in rat. It was found that baicalein formulated by SLN could increase the t1/2 and MRT by 1 hr, decrease the clearance and increase the AUC in plasma. The Cmax of baicalein-SLN was 5-fold higher than that resulted from baicalein-solution and thereby increased the plasma concentration. It was suggested that SLN could extend the period of baicalein in blood. High concentration of baicalein was found in the thalamus of the rat. It proved that baicalein could transport through the blood-brain barrier to consequently produce the antipyretic effect.

並列關鍵字

Scutellaria ； Antipyretic ； Solid lipid nanoparticles(SLN)

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