開發穿心蓮內酯奈米乳劑及其藥物動力學及抗發炎效果評估

Development and pharmacokinetic and anti-inflammatory evaluation of andrographolide nanoemulsion

陳怡蓁(Yi-Chen Chen)

指導教授 ： 吳育澤

高雄醫學大學/藥學院/藥學系碩士班/碩士(2016年)

摘要

本研究目的為製備及評估穿心蓮內酯奈米乳劑來改善穿心蓮內酯之口服生體可用率，並且利用之小鼠腸道發炎模型來測試穿心蓮內酯奈米乳劑的抗發炎效果。奈米乳劑的油相是利用Tocopherol與Ethanol混合，進而增加穿心蓮內酯溶解度從2.51提升至10.51 mg/mL，而乳化劑是選用 Cremophor EL。經由高速均質後，再利用高壓均質1500 bar, 6循環，製備成穿心蓮內酯奈米乳劑，成分含量為3.95 mg/mL，粒徑大小為132 nm，黏度為28 cp，安定性結果顯示，處方在4°C以及25°C可以儲存一個月。而利用Sprague- Dawley (SD) 大鼠腸道通透度試驗，穿心蓮奈米乳劑與懸浮液相比在十二指腸通透性提升5倍，空腸中提升8倍，迴腸提升7倍。藥物動力學實驗結果顯示，相較於穿心蓮內酯之懸浮液，穿心蓮內酯奈米乳劑與穿心蓮內指之懸浮液相比，提升其口服生體可用率達約6倍，最高血中濃度也提升高達14倍。抗發炎模式是利用C57BL/6品系小鼠，以indomethacin來誘導小鼠腸道發炎，評估潰瘍面積指數。實驗結果顯示，給予奈米乳劑之後，其潰瘍指數從18降為2，證明奈米乳劑具有較佳的抗發炎效果。

關鍵字

穿心蓮內酯 ； 奈米乳劑 ； 發炎性腸炎 ； 穿透度試驗 ； 藥物動力學

並列摘要

The aims of this present study were to prepare and evaluate of andrographolide (AG) nanoemulsion to enhance its oral bioavailability and examine the effect of AG nanoemulsion on murine experimental colitis induced by indomethacin. The formulation consisted of Tocopherol and ethanol as oil which could enhance AG solubility from 2.51 to 10.51 mg/mL, and Cremophor EL as surfactant. The nanoemulsion was first prepared by using high-speed homogenizer, and then used high-pressure homogenizer at 1500 bar for 6 cycles to form nanoemulsion. The drug content was about 3.95 mg/mL and the particle size was 132 nm with the viscosity of 28 cp. The AG nanoemulsion was stability at 4°C and 25°C for three month according to the stability test. The permeability study indicated that AG nanoemulsion could increase 5 times in duodenum and 8 times in jejunum and 7 times in ileum compared to AG suspension. Pharmacokinetics study showed that AG nanoemulsion could increase bioavailability about 6 times and Cmax about 14 times compared to the unformulated AG suspension. C57BL/6 mice was used in anti-inflammatory modle on colitis induced by indomethacin. And to assess the ulcer index. According to the result of pharmacodynamics study, the ulcer index was down from 18 to 2, it indicated that the AG nanoemulsion had great potential to treat gastrointestinal inflammatory disorders.

並列關鍵字

andrographolide ； nanoemulsion ； oral bioavailability ； inflammatory bowel disease

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