摘要
本课题主要制备了用于口腔黏膜给药的华夏小葱提取物亚微乳,并初步评价了其对大鼠急性心肌缺血的药效作用。以丹参酮ⅡA为模型药物,通过体外透黏膜实验研究了载药亚微乳的透黏膜行为。主要结果如下:(1)对华夏小葱提取物亚微乳处方进行筛选,分别采用超声法和高压匀质法制备亚微乳,并进行了工艺优化,初步考察了华夏小葱提取物亚微乳的稳定性。结果表明,采用高压匀质法制得的华夏小葱提取物亚微乳具有较好的稳定性,其平均粒径为162.8 nm。(2)制备了以Poloxamer 407为基质的华夏小葱提取物亚微乳原位凝胶,当Poloxamer 407含量为14%和14.5%时,其相应的相变温度分别为37.1±0.3℃和32.5±0.4℃,这提示华夏小葱提取物亚微乳原位凝胶可在口腔内能形成凝胶。(3)通过动物实验比较华夏小葱提取物亚微乳与华夏小葱提取物油溶液对大鼠急性心肌缺血的药效作用。结果表明,小葱亚微乳药起效快,5 min内起效,而华夏小葱提取物油溶液起效时间为10～15 min;两者在ST段值变化上没有显著性差异,药效作用相似。(4)以丹参酮ⅡA为模型药物,采用高压匀质法制备了丹参酮ⅡA的亚微乳,比较了丹参酮ⅡA亚微乳和对照油溶液的透黏膜行为,结果表明,丹参酮IIA亚微乳在15 min即有药物透过黏膜,其在第3 h的累积透黏膜量达到10.8μg(黏膜面积为3.0 cm2),而对照品溶液在第2 h才透过黏膜,在第3 h的累积透黏膜量仅为2.44μg(黏膜面积为3.0 cm2)。亚微乳有效促进了难溶性药物透黏膜吸收,具有透黏膜速度快,时滞短的特点。
The submicroemulsions of extract of Chinese Allium fistulosum L.were prepared and the pharmacodynamic effects on the rats with acute myocardial ischemia were studied. Tanshinone IIA as a model drug was incorporated into submicroemulsions and their mucosal absorption experiments were performed to evaluate the buccal delivery of Tanshinone IIA using submicroemulsions. The main results are as follows:
(1) The extract of Chinese Allium fistulosum L. (ECAF) was loaded into the various submicroemulsions. The high-pressure homogenization and ultrasonic method were used to prepare ECAF-loaded submicroemulsions and the optimum process was obtained. The submicroemulsion prepared by high-pressure homogenization had good stability. The average diameter of submicroemulsion was 162.8 nm and its polydispersity index (PDI) was 0.156. (2) Poloxamer 407 as a in situ gel matrix was used to construct submicroemulsion-based in situ gel. When the contents of Poloxamer 407 were 14% and 14.5% in gel, their phase transfer temperature was 37.1±0.3℃and 32.5±0.4℃, respectively. It implies that it is possible for submicroemulsion-based in situ gel to form high viscous gel in the oral cavity. (3) The pharmacodynamic effects of ECAF-loaded submicroemulsions and ECAF oily solution on rats with acute myocardial ischemia were compared. The results showed that ECAF-loaded submicroemulsions led to a rapid pharmacodynamic effect in 5 min, but ECAF oily solution only showed similar effect after 10 or 15 min. There were no significant differences between groups on the value of S-T segment and both had similar pharmacodynamic effect. (4) Tanshinone IIA as a model drug was also incorporated into submicroemulsions using high-pressure homogenization. The mucosal absorption experiments were performed to evaluate the buccal delivery of Tanshinone IIA from submicroemulsions and oil solutions, respectively. The results showed that the submicroemulsions could penetrate through mucous membrane in 15 min. The accumulative amount of Tanshinone IIA from submicroemulsions was 10.8μg in 3.0 cm2 area. The oily solution could only penetrate through mucous membrane after 120 min and the accumulative amounts of Tanshinone IIA from solution were 2.44μg in 3.0 cm2 area. The submicroemulsion has a powerful ability to enhance the buccal delivery of lipophilic drugs and can lead to a high permeation rate with short time lag.
引文
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