中南药学

目的 制备罗通定微乳凝胶(L-THP-MBG)并进行体外评价和初步药效学考察。方法 采用伪三元相图法初步筛选罗通定微乳(L-THP-ME)处方，通过D-最优混料设计优化L-THP-ME处方，并对其结构、粒径和电位进行表征；选用卡波姆940作为基质，采用直接溶胀法制备L-THP-MBG。采用Franz扩散池和流变仪对L-THP-MBG进行体外经皮渗透性和流变性能考察，并通过热板实验和醋酸扭体实验初步考察其镇痛作用。结果 L-THP-ME最佳处方为：油酸乙酯-(EL40∶PEG400=2∶1)-水=5∶34∶61，微乳呈球形或类球形，粒径为(19.64±0.46)nm，Zeta电位为(-8.91±1.11)mV；L-THP-MBG 24 h体外累积渗透量为(177.62±5.70)μg·cm-²，渗透速率为罗通定亲水凝胶(L-THP-G)的2.2倍。流变学结果显示，L-THP-MBG为假塑性流体，弹性模量大于黏性模量，呈稳定的半固体状态。药效学结果表明，L-THP-MBG能显著提高热板痛阈值，抑制醋酸所致扭体反应。结论 L-THP-ME粒径大小符合经皮给药要求，L-THP-MBG具有良好的体外经皮渗透性和镇痛作用，可为罗通定开发成经皮给药制剂提供参考。

Objective To prepare L-tetrahydropalmatine microemulsion-based gel (L-THP-MBG) and conduct in vitro evaluation and preliminary pharmacological investigation.Methods The pseudo-ternary phase diagram method was used to preliminarily screen the formula of L-tetrahydropalmatine microemulsion (L-THP-ME).The L-THP-ME formula was optimized by D-optimal mixture design and characterized in terms of structure,particle size and potential.Carbomer 940 was used as a substrate to prepare L-THP-MBG by direct solubilization method.The in vitro transdermal permeability and rheological properties of L-THP-MBG were examined with a Franz diffusion cell and rheometer.Its analgesic effect was also initially examined by hot plate test and acetic acid torsion test.Results The optimal formula of L-THP-ME was ethyl oleate-(EL40∶PEG400=2∶1)-water=5∶34∶61.The microemulsions were spherical or globular,with a particle size of (19.64±0.46) nm and a Zeta potential of (-8.91±1.11) mV.The 24 h in vitro cumulative permeation of L-THP-MBG was (177.62±5.70) μg·cm-²,which was 2.2 times higher than that of L-tetrahydropalmatine gel.The rheological results showed that L-THP-MBG was a pseudoplastic fluid with elastic modulus greater than viscous modulus and in a stable semi-solid state.Pharmacodynamics showed that L-THP-MBG significantly increased hot plate pain threshold and inhibited acetic acid-induced torsion response.Conclusion The particle size of L-THP-ME meets the requirement of transdermal drug delivery,and L-THP-MBG has good in vitro transdermal permeability and analgesic effect,providing a basis for the development of L-tetrahydropalmatine into transdermal drug delivery formulation.