α-萜品醇脂肪酸酯对美洛昔康经皮促渗透作用的考察

发布时间：2018-08-25 12:39

【摘要】：目的:本研究以α-萜品醇为先导化合物与饱和直链脂肪酸合成系列萜品醇酯衍生物,包括:丁酸萜品醇酯(T-BUT)、己酸萜品醇酯(T-HEX)、庚酸萜品醇酯(T-HEP)、癸酸萜品醇酯(T-DEC)、月桂酸萜品醇酯(T-DOD)、肉豆蔻酸萜品醇酯(T-TET)、硬脂酸萜品醇酯(T-STE)、油酸萜品醇酯(T-OA),并考察α-萜品醇酯类衍生物对美洛昔康(MLXC)的促透活性。方法:采用双室扩散池以离体兔皮为屏障进行体外渗透实验,系统考察了合成萜品醇酯及常用促透剂[N-甲基吡咯烷酮(NMP)、月桂氮卓酮(azone)、薄荷醇(M)]在肉豆蔻酸异丙酯(IPM)系统和压敏胶型贴剂系统中对MLXC渗透行为的影响。结果:与不加促透剂(空白)相比,浓度为5%的α-萜品醇,T-BUT,T-HEX,T-HEP,M及NMP对MLXC均有显著的促透作用(P0.05);与萜品醇相比,NMP和T-HEX的促渗作用均显著提高(P0.05);而制成压敏胶分散型(DIA)贴剂后,仅α-萜品醇,T-HEX,M,NMP表现出促透作用(P0.05),当5%NMP与5%T-HEX联用时,MLXC的8 h累积透过量是空白组的5.08倍。结论:合成的α-萜品醇脂肪酸酯对MLXC有显著促透作用,有望成为一种有应用价值的促透剂。
[Abstract]:OBJECTIVE: To synthesize a series of terpene alcohols derivatives, including terpene butyrate (T-BUT), terpene hexanoate (T-HEX), terpene heptanoate (T-HEP), terpene decanol ester (T-DEC), terpene Laurate alcohol ester (T-DOD), terpene myristate alcohol ester (T-TET), terpene stearate alcohol, using alpha terpene alcohols as precursors and saturated linear fatty acids. T-STE, T-OA, and the permeation enhancements of alpha-terpene alcohol ester derivatives to meloxicam (MLXC) were investigated. METHODS: In vitro permeation experiments were carried out in a two-compartment diffusion cell with isolated rabbit skin as barrier. The synthetic terpene alcohol esters and common permeation enhancers [N-methylpyrrolidone (NMP), lauroxone (azone), menthol (M) were systematically investigated. Results: Compared with those without penetration enhancer (blank), 5% alpha-terpene alcohol, T-BUT, T-HEX, T-HEP, M and NMP had significant penetration enhancements on MLXC (P 0.05), and NMP and T-HEX had significant enhancement on the permeability of MLXC (P 0.05). When 5% NMP was combined with 5% T-HEX, the cumulative permeability of MLXC at 8 h was 5.08 times that of the blank group. Conclusion: The synthesized fatty acid esters of alpha-terpene alcohol can significantly promote the permeability of MLXC and may be a valuable permeation enhancer.
【作者单位】： 华北理工大学药学院;唐山市妇幼保健院药剂科;唐山市新型药物制剂与释药技术重点实验室;
【基金】：国家自然科学基金(81603039) 河北省自然科学基金(H2013209098)
【分类号】：R943
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本文编号：2202913