Systemic delivery of alpha-asarone with Kolliphor HS 15 improves its safety and therapeutic effect on asthma

Abstract

The commercially available alpha-asarone injections (CA-ARE) were frequently found to cause severe anaphylactic reactions by the solubilizer contained in the formulation such as polysorbate 80 and propylene glycol. This study aimed to develop a new ARE injection using Kolliphor HS 15 as solubilizing agent (HS 15-ARE) by the dissolution method to resolve its poor solubility problem and reduce the anaphylaxis of CA-AREs caused by Polysorbate 80. The HS 15-ARE micelle showed a homogeneous round shape with the mean particle size of around 13.73?±?0.02?nm, polydisperse index (PDI) of 0.19?±?0.01 and solubilizing efficiency of 95.7%?±?2.4%. In vitro and in vivo studies showed that HS 15-ARE is a stable injection presenting the same pharmacokinetic profile with CA-ARE. Moreover, improved therapeutic effect was observed for HS 15-ARE in treating asthma compared to CA-ARE (p?<?0.05) with no anaphylactic reactions observed. These results demonstrate that the new formulation of ARE (HS 15-ARE) has a great potential for replacing CA-AREs injections.     

α-细辛脑防治青霉素诱导大鼠癫痫发作实验研究

目的观察α-细辛脑对青霉素诱导大鼠癫痫急性发作的作用并分析其抗癫痫的作用机制。方法将wistar大鼠随机分成正常对照组、模型对照组和药物实验组,正常对照组和模型对照组大鼠腹腔注射生理盐水,药物实验组腹腔注射α-细辛脑,20min后模型对照组和药物实验组注射青霉素（480万U/kg）诱导大鼠癫痫发作。观察并比较3组大鼠的行为变化情况,比色法检测大鼠脑组织中超氧化物歧化酶（SOD）、丙二醛（MDA）含量,ELISA方法检测白细胞介素1β（IL-1β）与肿瘤坏死因子（TNF-α）含量。结果α-细辛脑可使癫痫大鼠发作程度减轻和发作潜伏期延长;使癫痫大鼠脑内MDA、TNF-α和IL-1β含量明显降低,SOD活性明显升高。结论α-细辛脑可有效地防治癫痫的发作并有效地改善癫痫大鼠的预后情况。其抗癫痫作用与调节脑组织的相关因子、提高其脑组织清除自由基、增强抗氧化作用有着密切关系。