丹参酮Ⅱ_(A)-甘草次酸固体脂质纳米粒的制备及其对痤疮的抑制作用研究  

Preparation of tanshinone Ⅱ_(A)-glycyrrhetinic acid solid lipid nanoparticles and its inhibitory effect on acne

作　　者：陈芳宁 王秀丽[1] 许蕊蕊 王晓杰[2] 阮婧华 CHEN Fang-ning;WANG Xiu-li;XU Rui-rui;WANG Xiao-jie;RUAN Jing-hua(Bejjing University of Chinese Medicine,Beijing 102488,China;College of Bioengineering,Bejjing Polytechnic,Beijing 100176,China;Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China)

机构地区：[1]北京中医药大学,北京102488 [2]北京电子科技职业学院生物工程学院,北京100176 [3]贵州中医药大学,贵州贵阳550001

出　　处：《中国中药杂志》2022年第9期2449-2456,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81202928,82060643);北京市自然科学基金项目(7123118);贵州省科技厅社会发展计划项目[黔科合支撑(2018)2821]。

摘　　要：筛选丹参酮Ⅱ_(A)-甘草次酸固体脂质纳米粒(GT-SLNs)的最优处方工艺,进行体内外评价,并考察该制剂口服后对痤疮的影响。运用单因素及效应面法优化制备工艺及处方并进行验证;UPLC测定GT-SLNs中甘草次酸(GA)及丹参酮Ⅱ_(A)(TSN)的体外释放过程;通过小鼠体内性激素水平、耳肿胀模型及皮脂腺组织变化考察脂质纳米粒口服后对痤疮的影响;进行药代动力学评价。筛选出脂质纳米粒的优化处方;GT-SLNs中GA及TSN的24 h累积释放率分别为65.87%±5.63%、36.13%±2.31%;口服GT-SLNs及甘草次酸-丹参酮Ⅱ_(A)混合溶液(GT-Mix)后,GT-SLNs中TSN的AUC_(0-t)及AUC_(0-∞)分别为原药组的1.98、4.77倍,SLNs组TSN的峰值浓度为原药组的17.2倍;灌胃给予GT-SLNs后,小鼠血清中的睾酮水平均有明显下降,GT-SLNs中睾酮与雌二醇比值均显著降低,且小鼠的皮脂腺体有一定程度的萎缩。结果表明,得到的包封率良好,粒径均匀的固体脂质纳米粒对GA及TSN具有促进释放的作用;GT-SLNs可以针对雄激素增多、皮脂腺分泌异常及炎症损害这两方面的痤疮起到一定的治疗作用。The optimal prescription of tanshinone Ⅱ_(A)(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.

关 键 词：痤疮 丹参酮Ⅱ_(A)甘草次酸 固体脂质纳米粒 处方筛选 

分 类 号：R283.6[医药卫生—中药学]