【摘要】：目的:本研究以α-萜品醇為先導(dǎo)化合物與飽和直鏈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-萜品醇酯類衍生物對美洛昔康(MLXC)的促透活性。方法:采用雙室擴(kuò)散池以離體兔皮為屏障進(jìn)行體外滲透實(shí)驗(yàn),系統(tǒng)考察了合成萜品醇酯及常用促透劑[N-甲基吡咯烷酮(NMP)、月桂氮卓酮(azone)、薄荷醇(M)]在肉豆蔻酸異丙酯(IPM)系統(tǒng)和壓敏膠型貼劑系統(tǒng)中對MLXC滲透行為的影響。結(jié)果:與不加促透劑(空白)相比,濃度為5%的α-萜品醇,T-BUT,T-HEX,T-HEP,M及NMP對MLXC均有顯著的促透作用(P0.05);與萜品醇相比,NMP和T-HEX的促滲作用均顯著提高(P0.05);而制成壓敏膠分散型(DIA)貼劑后,僅α-萜品醇,T-HEX,M,NMP表現(xiàn)出促透作用(P0.05),當(dāng)5%NMP與5%T-HEX聯(lián)用時,MLXC的8 h累積透過量是空白組的5.08倍。結(jié)論:合成的α-萜品醇脂肪酸酯對MLXC有顯著促透作用,有望成為一種有應(yīng)用價值的促透劑。
[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.
【作者單位】： 華北理工大學(xué)藥學(xué)院;唐山市婦幼保健院藥劑科;唐山市新型藥物制劑與釋藥技術(shù)重點(diǎn)實(shí)驗(yàn)室;
【基金】：國家自然科學(xué)基金(81603039) 河北省自然科學(xué)基金(H2013209098)
【分類號】：R943
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本文編號：2202913