【作者】 叶盛英；

【导师】 高文远；

【作者基本信息】 天津大学 ， 应用化学， 2009， 博士

【摘要】 “红花洗药”是解放军第254医院自行研制的中药散剂,批准制剂文号为北制字(2006F12010),适用于跌打损伤、风湿疼痛,筋骨酸痛,关节肿痛等。在临床应用至今已有二十几年,疗效确切,未见不良反应发生。但“红花洗药”的剂型老化,使用、携带不便,生物利用率低,起效慢。本文在原组方不变的情况下,研究“红花洗药”的新剂型-“消淤止痛喷雾剂”。首先研究了“消淤止痛喷雾剂”的制备工艺,发现乙醇提取样品比水提取样品中羟基红花黄色素A、山奈素(君药红花)、欧前胡素(臣药白芷)、齐墩果酸(臣药威灵仙),几个检测成分含量均高;样品抗炎镇痛作用明显,确定了乙醇做新制剂的提取溶媒。采用正交实验方法,对“消淤止痛喷雾剂”的制备工艺中渗漉工艺进行优化。最佳提取制备工艺:50%浓度乙醇、浸泡时间48h、渗漉速度为5 mL/min、收集6倍渗漉液。研究了“消淤止痛喷雾剂”质量控制标准,其中红花、白芷、当归、川芎4味药物进行薄层色谱鉴别研究,采用高效液相色谱法监控红花中羟基红花黄色素A的含量。研究了“消淤止痛喷雾剂”的稳定性,“消淤止痛喷雾剂”在室温(25°C)条件下放置稳定性良好,有效期可暂定1年。药效实验表明“消淤止痛喷雾剂”对热刺激所致疼痛感觉具有明确对抗作用,与云南白药气雾剂镇痛作用相当。具有明确的对抗实验性急性炎症的活性,与云南白药气雾剂和氟轻松抗炎作用相当。经过皮肤急性毒性、皮肤刺激性实验和皮肤过敏实验等观察,表明本制剂毒性甚小,是一种安全性较好的外用制剂。此外本文对“消淤止痛喷雾剂”药效物质基础进行了初步研究。羟基红花黄色素A(HSYA)是其最重要的有效成分。研究结果表明HSYA对体外缺氧诱导的神经细胞损伤和体内短暂局灶性脑缺血再灌注损伤具有神经保护作用,这种保护作用是由于HSYA抑制了部分局灶性缺血再灌注损伤后的炎症反应与抑制促炎细胞因子的效应有关。更多还原

【Abstract】 “Honghua xiyao”(2006F12010) ,a powder of traditional Chinese medicine, is made by PLA No.254 hospital .It has been used for 20 years to treat traumatic injuries, and pain due to wind-dampness. Because of its disadvantages such as inconvenient application method and carries due to aged dosage form, low bioavailability, slow effect and so on, new dosage form (Xiaoyuzhitong Spray) is developed on the base of the original prescription in the paper.The results of preparation procedure show that the contents of HSYA and kaempferide in Carthamus tinctorius, imperatorin in Angelica dahurica, oleanolic acid in Clematis chinensis are higher in extract of alcohol than those in extract of water. Moreever, the analgesic effect of spray made by alcohol extract is conspicuous. Hence, alcohol is used as extraction solvent in the new praeparatum. Percolate technology in preparation procedure is optimized by utilizing orthonal design method. Optimal extraction technology conditions are 50% alcohol, soak time 48h, percolate speed 5mL/min, 6 times of percolate. Quality control standard of spray is established. Carthamus tinctorius, Angelica dahurica, Angelica sinensis and Ligusticum chuanxiong are detected by TLC and the content of hydroxyl safflower yellow pigment (HSYA) is monitored by HPLC. Its term of validity is one year in room temperature (25°C) .Pharmacodynamic action experiment shows that spray on pain perception due to heat stimulation is definite antagonistic effect and spray in analgesic effect corresponds to Yunnan white powder aerosol. Spray has definite anti-acute inflammation activity. Spray in anti-inflammatory effect corresponds to Yunnan white powder aerosol and Fluocinolone. The result of skin acute toxicity, skin stimulus, skin allergic experiments and others show that the spray is a safe preparation for external use due to its low toxicity.In addition, therapeutic basis of spray is studied preliminarily in the paper. The hydroxyl safflower yellow pigment (HSYA) is the most important effective component in Carthamus tinctorius. The results show that in vitro hypoxia-induced nerve cell damage in the body and a short focal cerebral ischemia-reperfusion injury HSYA has a neuroprotective effect, it attributes protective effect of HSYA to suppressing partly inflammation response induced by the focal ischemia-reperfusion injury and suppressing pro-inflammatory cytokines effects.更多还原