水蔓菁总黄酮提取纯化及滴丸成型工艺研究

【作者】 杜艳；

【导师】 丁红；

【作者基本信息】 山西医科大学 ， 药剂学， 2006， 硕士

【摘要】 水蔓菁是传统的清热解毒中药,为玄参科细叶婆婆纳属水蔓菁Veronica linariifolia pall.ex link subsp.dilatata(Nakai et Kitag.)Hong ,为常用中药。具有清热解毒、利尿、止咳化痰等作用。临床用于治疗慢性气管炎、肺化脓症、咳吐脓血、急性肾炎、尿路感染。本文以水蔓菁总黄酮(按芦丁折算)提取物为有效成分,对水蔓菁药材进行提取、分离、纯化研究,将有效成分总黄酮制成水蔓菁滴丸。采用可见分光光度法,对水蔓菁总黄酮的含量进行控制。考察了方法的线性、精密度、稳定性、重现性和回收率,证明该方法稳定、可行。提取方法比较了水回流、水超声、醇回流和醇超声等方法。确定采用水回流提取法。应用正交设计优选出最佳提取工艺:水、10倍量、3次、1h/次。用大孔树脂法对水蔓菁提取物的总黄酮进行富集,筛选了大孔树脂的种类,综合考察了树脂的吸附率、解吸率、上样浓度、上样流速、水洗体积、流速、醇洗脱浓度、体积、流速等各项指标。确定最佳纯化工艺为:使用HPD600型大孔树脂,上样溶液为药液比1:8的水蔓菁提取液,以1.5BV·h-1的速度上样至泄漏,然后用2 BV的水以2BV·h-1的流速洗,再用4BV的50%乙醇洗脱,流速为2BV·h-1,将洗脱液浓缩,干燥为浸膏,即得水蔓菁纯化物,总黄酮的含量达到20%以上。采用熔融法制备水蔓菁滴丸,确定了处方。对影响因素:滴速、熔融温度、冷凝液高度、滴头口径、药物与基质配比等进行单因素考察,用正交设计优选滴丸制备工艺:水蔓菁纯化物与PEG4000配比为1:2,药液熔融温度80℃,保温温度65℃,滴速40d·min-1,滴距6cm,冷凝液为甲基硅油,冷凝液高度为35cm,滴头内外径为3.0/4.0mm,冷凝剂温度0℃~ 5℃。所得滴丸平均丸重40mg。进行稳定性试验,结果表明制备的水蔓菁滴丸处方稳定、质量可控,达到制剂设计目的和要求。对水蔓菁滴丸进行质量标准研究,建立了有效成分总黄酮的含量测定方法。为该制剂提供了可靠的质量控制方法。首次运用大孔吸附树脂富集水蔓菁中总黄酮,使其总黄酮达到20%以上,而传统水提工艺提取的总黄酮含量仅为7%,新方法富集的总黄酮含量大大提高;其次将纯化物制成滴丸新剂型,并初步进行了水蔓菁滴丸的质量考察。更多还原

【Abstract】 Veronica linariifolia is a commonly used for removing heat and toxic substance. It is belonged to Veronica linariifolia pall.ex link subsp.dilatata(Nakai et Kitag.)Hong.It have the function of removing heat, diuresis, relieving a cough and coveting sputum. It can cure tracheitics, lung fester, anxious nephritis, urine infection.This experiment aimed to distill, separate, purify Veronica linariifolia and develop a new medicine named Veronica linariifolia drop pill, the effective component of which is the total flavone. The determination of total flavone of the extraction is controlled by visible spoctrophotometry. This paper review the lineanity, exactitude, stability, recur and callback of the method. It prove the method stable.This paper compare the method of water circumfluence, water ultrasonic, ethanol circumfluence, ethanol ultrasonic. This paper use water circumfluence to extract total flavone. Orthogonal test was used to choose optimum extractive method. The optimum extraction procedures are as follows: Optimum extractive solvent :water ;Solvent volume: 10 times of extractive solvent; Extractive time: 1.0 hour each time; Extractive number of times: 3 times. This paper study on purification process of total flavone with macroreticular resin and choose the type of macroreticular resin, review the absorption ratio, desorption ratio, liquor’s chroma, velocity, water’s volume, velocity, ethanol’s volume, volume, velocity.The best technics of purification is as follows: the type of macroreticular resin is HPD600, the sample fluid (1:8), the velocity is 1.5BV/h,the water is 2BV with velocity of 2BV/h, 50% ethanol is 4BV with velocity of 2BV/h, then concentrate the fluid ,dry it, the intermediate contain 20 percent total flavone.This paper use melting method to prepare Veronica linariifolia drop pill, study on the influencing factors: the velocity of dropping, the temperature of melting, and the length of condensation pole, diameter of burette, the ratio of medicament and PEG4000, then find the best technics with orthogonal test: the ratio of drug and PEG4000 is 1:2,the melting temperature is 80℃,the temperature of heat preservation is 65℃,dropping velocity is 40d/min,the dropping distance is 6cm,the condensate is silicon oil, the length of condensation pole is 50 cm, the inside and outside diameter of drop head is 3.0/4.0 mm, the temperature of refrigerant is 0~5℃. The average weight of drop pill is 40mg.Doing the stability test, the result show that the prescription of Veronica linariifolia drop pill is stable, the quality is controlled. So it accord with the purpose and request of preparation design. This paper research quality standard of the drop pills of Veronica linariifolia, establish the determination of flavone.This paper purifies total flavone of Veronica linariifolia with macroreticular resin for the first time, the content of flavone is above 20%, compared with traditional craftwork, the content of flavone is improved greatly. Then crank flavone out drop pill, and establish a suit of scientific更多还原