连花芳粉针制备工艺及质量标准研究

【作者】 余超；

【导师】 倪健；

【作者基本信息】 北京中医药大学 ， 中药制剂学， 2004， 硕士

【摘要】 目的:流感是迄今仍未被人类有效控制的病毒性传染病,由于病毒的不断变异,种类不断变化,人类合成化学药的速度远赶不上病毒变异的速度。因而从植物药(中药)中寻找高效、低毒的抗流感病毒药物已得到世界各国的重视。本课题组在对清热解毒复方研究中,筛选发现中医经验方连花芳 1 号方(重在解表)与 2号方(重在清里热)的有效部位具有显著的抗病毒、抗菌、解热、抗炎、镇痛等作用,特别是注射用药在剂量大大减小的情况下,仍显示出显著的药效作用。因此,本论文将对此两方进行粉针制剂学的基础研究,为研究中药复方(有效部位)粉针剂技术进行探索,为进一步研究开发中药创新药物奠定基础。方法: 1)制剂工艺研究:通过正交试验优选药物有效部位的最佳提取工艺;采 (用大孔吸附树脂分离技术分离纯化药物有效部位;采用环糊精包合技术将薄荷油制备成 HP-β-CD 包合物;采用冷冻干燥技术制备连花芳粉针剂,并对连花芳 1 号方和 2 号方的冻干成品进行制剂学筛选;(2)质量标准研究:采用 HPLC 法对连翘苷、连翘酯苷、绿原酸、栀子苷、牛蒡子苷、黄芩苷进行定量测定;采用 TLC法对连花芳各药物进行定性鉴别;(3)初步稳定性研究:采用留样观察法考察连花芳成品的稳定性,并通过试验结果对 1 号方和 2 号方进行再次筛选。结果:(1)通过工艺筛选,确定金银花有效部位的制备工艺为:药材用 10 倍量乙醇回流提取 3 次,每次 1hr,合并提取液,滤过,滤液回收乙醇,浓缩至浓度为相当于生药量 50mg/mL 后,调 pH 值,以 1mL/min 的流速通过径高比为 1/10 的大孔吸附树脂柱,上样体积为 5.6BV,用 4BV 乙醇以 1mL/min 的流速进行洗脱,洗脱液回收乙醇,减压浓缩至干,得干浸膏,备用;将薄荷油制备成 HP-β-CD 包合物后,大大增加了其在水中的溶解度,其制备工艺为:取 1 份薄荷油和 8 份HP-β-CD,用研磨法在 45℃下研磨包合 60min 后,45℃减压干燥,少量石油醚洗涤,即得;用冷冻干燥技术成功地将连花芳 1 号方和 2 号方制备成粉针剂,成品质量合格。(2)初步建立了连花芳粉针的质量标准,其方法灵敏度高、准确性大、重复性好、专属性强。经含量测定,1 号方和 2 号方中指标成分的总含量分别为29.73%和 36.67%,符合要求;(3)初步稳定性试验表明:连花芳 1 号方和 2 号方制剂均比较稳定,可保证临床用药的质量。结论:通过制剂学基础研究表明,用冷冻干燥技术将中医经验方连花芳 1 号方与2 号方的有效部位制备成粉针剂均是可行的,其质量是稳定可控的,这为中药复方(有效部位)制成粉针剂提供了有价值的参考依据,为进一步研究开发中药创新药物奠定了基础。本研究达到了课题原设计的预期目的。更多还原

【Abstract】 Objective: Influenza is a kind of virus epidemic which has not beenthoroughly controlled until recent times. Due to the virus` continuousaberrance and transformation, it is hard for compound chemical medicinesto cope with that just in time. Therefore, National governments have paiedclose attentions on effective anti-influenza medicines by means of TCMfeaturing low toxin content. In our research of TCM composite formulasfor clearing away heat and toxic material, Chinese empirical prescriptionLianhuafang No.1 and No.2 filtered out. Here, No.1 is mainly for relievingexterior syndrome and No.2 subduing internal heat. And it is demonstratedthat both are anti-virus, anti-bacteria as well as anti-inflammation, andaffect markedly in reducing fever and subduing pains. Especiallyinjections in small doses can still perform remarkably well. Hence thedissertation will focus on the basic research of sterilized powder forinjection of Lianhuafang No.1 and No. 2, and hopefully, make contributionsto TCM innovations in the way of exerting the technology of sterilizedpowder for injection on TCM composite formula.Methods: (1) Study on process technology: Optimum extraction factors forchoosing the most effective parts of herbals were determined by crossingdesigns and comparative experiments. The macro absorption resins wereapplied to separate and purify the effective part. In order to enhancethe solubility of oleum menthae dementholatum ,it was prepared into aHP-β-CD by means of CD technology. Lianhuafang sterilized powder forinjection. were made by the freeze-dried technic and the finished productswere selected by pharmaceutical procedure according to their color,dissolvability, clarity and forms. (2) The study on quality specification:By using HPLC we have made quantitative analysis on Phillyrin,Forsythiaside, Arctiin, Gardenoside, Baicalin,Chlorogenic acid; By usingTLC we have made qualitative analysis on each constitute of Lianhuafang.(3) The preliminary stability investigation: through observing the remainspecimen ,we studied the properties, contents, sanitation and then chooseagain on the basis of stability results.Results:(1) Through procedure selection, the best processing method toprepare the effective part of honeysuckle was determined. It has greatly<WP=6>Abstract Ⅴincreased the solubility of oleum menthae dementholatum when prepared intoa HP-β-CD by means of CD technology and also offer a possibility to prepareinto sterilized powder for injection.Through procedure selection, theeffective part of Lianhuafang No.1 and No.2 can be prepared into sterilizedpowder for injection by means of freeze-drying technics and the propertiesof finished products are of good quality. (2) The quality specificationof Lianhuafang sterilized powder for injection: the method is mature,sensitive, accurate, repeatable and specific. The finished productsaccord with the requirements of TCM injections in common terms. The overallcontent of No.1 and No.2 is 36.67% and 29.73% respectively. (3) Thepreliminary stability investigation shown: the both Lianhuafang No.1 andNo.2 are stable in their quality and can meet the quality that clinicalmedicine required.Conclusion: According to the research of pharmacy, it was proved to befeasible to prepare the effective part of Lianhuafang No.1 and No.2 intosterilized powder for injection by means of freeze-drying technics. Italso supplies a valuable reference for other TCM empirical prescriptionsand lays the foundation for the future development of TCM composite formulaand TCM pharmaceutical research.更多还原