【作者】 赵琰玲；

【导师】 潘金火；

【作者基本信息】 南京中医药大学 ， 中药学， 2007， 硕士

【摘要】 头痛宁鼻腔喷雾剂是临床使用多年的中药复方制剂，用于治疗偏头痛、感冒头痛、血管神经性头痛等。我们按药品注册管理办法的要求，采用现代科技手段，对制备工艺、质量标准及稳定性进行了系统而全面的研究，具体研究内容包括以下几个方面：1．文献研究：以中医药理论为指导，全面阐述了本方的来源、研究概况及立题目的和意义，同时，对鼻腔给药的研究情况进行了归纳与总结。2．工艺研究：对处方药材的挥发油提取工艺、水煎煮工艺及醇沉工艺进行正交优选，得出挥发油提取最佳工艺：将药材(川芎和防风)粉碎过8目筛(其余直接用饮片)，加10倍量的水，浸泡1小时，煎煮5小时；水煎煮提取最佳工艺：加10倍量的水，提取2次，时间为1.5小时。醇沉的最佳工艺：药液浓缩至1：1，冷却至室温，加乙醇使含醇量达80％，静置8小时，抽滤。又以鼻腔喷雾剂的澄明度，稳定性，pH值，挥发油分散的均匀性及实际生产中的可操作性等为指标，通过平行试验和正交试验，优选了主要辅料的品种、配比及用量，通过优选，最后确定的成型工艺为：用优选工艺提取净化后的药液加入蒸馏水至1：2(1mL药液含0.5g生药)，2～5℃冷藏12小时，抽滤，滤液中加入挥发油、规定量的聚山梨酯80、亚硫酸氢钠、山梨酸钾等，加水制成规定量，搅拌均匀，用5％的氢氧化钠调pH值至6.0，分装，即得。3．质量控制方法研究：以鼻腔喷雾剂的pH值，喷射试验、装量及实际生产中的可操作性等为指标，建立了制剂通则检查项目。以阿魏酸对照品、白芷对照药材、防风对照药材以及薄荷对照药材为指标，分别建立了成品中川芎、白芷、防风以及薄荷四味药材的薄层定性鉴别方法。对制剂中的乌头碱进行了限量检查，分别以制剂中的乌头类总生物碱为指标，通过酸性染料比色法；以阿魏酸为指标，通过高效液相色谱法，分别建立了这两个指标含量测定方法，根据三批中试产品的测定结果，暂定本品每瓶含乌头类总生物碱不得低于0.9912mg，每瓶含阿魏酸不得低于60.6074μg。在上述研究的基础上，起草了头痛宁鼻腔喷雾剂的质量标准草案及质量标准草案起草说明书。4．稳定性研究：头痛宁鼻腔喷雾剂属于鼻用制剂，根据其理化性质和使用目的，参考2005年版《中国药典》一部附录Ⅸ鼻用制剂项下相关的要求，2005年版《中国药典》二部附录IR鼻用制剂项下鼻腔喷雾剂相关的要求，及《中药新药质量稳定性研究的技术要求》，按质量标准草案上制定的方法，对三批中试产品进行了初步稳定性考察，经过三个月的考察试验，证明各项指标均在合格范围内，说明头痛宁鼻腔喷雾剂在此包装条件下基本上是稳定的。更多还原

【Abstract】 The toutongning nasal spray are modern compound Chinese medicine that studied bychanging form of prepared drugs that used in clinic, which is used to cure hemicrania、megrim、and migraine. According to the standard of the Chinese new drugs, we studied itspreparation process, quality standard and preliminary stability systematically with modernscience and technology. The study details are as the following:1.Study on Literature: With the guidance of Traditional Chinese Medicine, the sourceof the prescription, the survey of the studies and the significance of developing the issue areelaborated widely. At the same time, we sum up the present research about cavum nasiadministration.2.Study on preparation process: With carrying on the volatile oil of the prescriptionmedicine material, the water decoction craft and ethanol to sink craft, by orthogonaldesign, we get a volatile oil to withdraw the best craft, The decoction of water withdrawsthe best craft and ethanol to sink the best craft. With the index of the clear degree ofpreparation, the pH worth, the even of volatile oil dispersion and the productivemaneuverability, and so on. the preparation forming technology was studied withparallel-contrast and orthogonal experiment. We select quality, mixture ratio, use level ofaccessories. We choose the preparation progress, the the end the make sure the of model thecraft is:The medicine of liquid joins the the distilled water to 1:2. joining the volatile oil,various of accessories, load separately, then get.3.study on quality control method: Establish the examination items of the preparationgeneral rules of toutongning nasal spray with recommend pH、weight differential andother indications. Set up the composition identified method of Ligusticum chuanxiongHort.. Radix angelicae dahuricae. Radix saposhnikoviae and Herba menthae by TLC.Establish a method for contend of Aconitine-type Alkaloid and ferulic acid determination intoutongning nasal spray by Acid-dye Colorimetry and HPLC. Stipulate the minimumlimit quantity of Aconitine-type Alkaloid and ferulic acid.On the basis of the above studies, we draw up the quality standard draft of toutongning nasal spray and it’s specification.4. Stability investigation: Because toutongning preparation belong to preparation ofcavum nasi administration, the stability test is carried out on the basis of the drug physicsand chemistry character and its applied purpose, referring to preparation of cavum nasiadministration items requirements of Pharmacopoeia of the People’s Republic of China(2005 Ed, Part 1, Appendix IX), nasal spray items requirements of Pharmacopoeia of thePeople’s Republic of China (2005 Ed, Part 2, Appendix IR)and the relative items in "Thetechnical requirement on new Chinese traditional medicine quality stability research".According to the quality standard draft of toutongning nasal spray, the preliminary stabilityinvestigation were carried on within three months, which showed that the indications werein the qualified range, and the tablets were stable in the condition of it’s packaging.更多还原