兒茶素微脂粒劑型之口服輸送系統研究

Development of liposomal formulation of catechin for oral delivery system

吳怡欣(Yi-Hsin Wu)

指導教授 ： 黃耀斌

高雄醫學大學/藥學院/藥學研究所/碩士(2009年)

https://doi.org/10.6832/KMU.2009.00027

摘要

有相當多研究報導說明自由基攻擊細胞所產生的代謝產物與老化速率以及許多疾病的形成有明顯的相關性。所以抗氧化劑是可對抗自由基且避免對人體的氧化性傷害，進而減少慢性疾病的產生。現今許多文獻指出兒茶素具有許多生理活性，不但可清除自由基，還可抗發炎、抗病毒、抗菌、抗突變與抗癌。然而兒茶素口服生體可用率非常低(2~5%)，清除率也極高，因此本研究藉由liposomes之處方劑型來提高口服生體可用率，並延長藥物在血漿中之作用時間。
我們利用Epikuron 200之磷脂質，以及膽固醇(cholesterol)作為製備微脂粒處方之材料，並探討處方不加或分別加入表面修飾劑stearylaminem與dicetyl phosphate以及非離子界面活性劑Tween 80對處方之影響，且比較此三組微脂粒的物理性質，包含包埋率、粒徑大小以及處方在第0、14、21、30天之安定性的變化，進一步篩選出理想之處方。此三組所製備出的微脂粒平均粒徑大小為35~65 nm，包埋率在50~80%之間。體外釋放試驗顯示，其最佳處方在第12小時之累積釋放量可達55%。
在篩選出理想之處方後，以口服給予(+)-Catechin 30 mg/kg於健康大鼠，並與溶液劑做比較，觀察大鼠體內血漿中藥物動力學情形以及腦部組織的分佈。結果發現經過微脂粒製備化的(+)-Catechin，其曲線下面積與生體可用率皆比溶液劑來得好。

關鍵字

兒茶素 ； 微脂粒 ； 藥物動力學

並列摘要

A lot of studies have proven that decay rate and many diseases obviously correlate with free radicals attack to living cells and its generated metabolic product. Hence antioxidants can against free radicals and avoid oxidative damages for human, and then decrease generation of chronic diseases. In recent years, numerous studies indicated that catechin not only remove free radicals but has various types of pharmacological properties such as anti-inflammatory, anti-viral, anti-bacterial, anti-mutagenic and anti-carcinogenic. However the oral bioavailability of catechin is known to be low (2~5%), and the systemic clearance is also high. The purpose of this experiment was to promote oral bioavailability of catechin with liposomal formulation and prolong duration time of drug in plasma.
We used phospholipid, Epikuron 200, and cholesterol as material to prepare liposome formulation, and discuss the effect of liposome formulation which contain phospholipid and cholesterol or the mix of ionic surfactants such as stearylamine, dicetyl phosphate and nonionic surfactant such as Tween 80. For the three group that physical properties of drug entrapment efficiency, particle size and stability of formulation on day 0, 14, 21 and 30 were respectively compared, and further, we were sieve out optimization of formulation. Preparation of three group of liposome that the mean diameters were 35~65 nm and the entrapment efficiency were 50~80%. According to in vitro release experiment result, the optimization of formulation, catechin accumulated amount was 55% at 12 hour.
After sieve out optimization of formulation, we using oral administration for health rats with dosage 30 mg/kg of catechin. Compared with catechin solution, we observed the pharmacokinetics and distribution in brain tissue. In vivo result, we found the area under the curve and bioavailability of catechin-liposome were better than solution.

並列關鍵字

catechin ； liposomes ； pharmacokinetic

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