Study On Preparation Process And Quality Standard Of The Congzhikeli Granules

The Congzhikeli granules is a new compound preparation of Traditional Chinese Medicine,which consists of Rhizoma Acori Tatarinowii and other seven herbs.It has the function of promoting qi circulation to remove dampness,regulating qi-flowing for eliminating phlegm,activating blood circulation to dissipate blood stasis,tonifying spleen and so on.In clinical practice,the Congzhikeli granules mainly for the prevention and treatment of Alzheimer's disease.Preliminary pharmacological experiments show that it can significantly increase the activity of rat hippocampus acetylcholine transferase and acetyl choline,and improve NOS neurons in the rat hippocampus damage,activate the cNOS activity,and promote the synthesis of NO and improve the content of NGF in AD brain tissue of rats,so that the rats memory has improved significantly.On this basis,subject to Traditional Chinese Medicine theory and application of modern pharmaceutical technology and research methods for its scientific and rational preparation process and quality standards,to ensure the safe and effective pharmaceutical preparations,the quality is stable and controllable,suitable for industrial production.1.Study on preparation processVolatile oil extraction process has been completed by the predecessors.Preliminary studies show that the volatile components and non-volatile parts from the prescription are effective components.Boiling in water,ethanol purification and preparation of molding process was the need for research.Boiled technology research:merger boiling the residue after the essential oil was extracted with the rest of medicine,by orthogonal test,Synephrine content,Verbascoside content of Ginsenosides Re,Rgl and Rbl content and extract yield evaluation index,study addwater,extraction time,extraction times on the effect of water extraction,thus the optimized water extraction process as follows:the first time plus 12 times the amount of water to soak for 1 h,reflux boiling 1.5h,the second time plus 10 times the amount of water reflux boiling 1h,the third time plus 8 times the amount of water reflux boilinglh.The average levels of Synephrine,Mullein Glycoside,ginsenoside Re,Rgl and Rbl were 4.435mg/g,0.226mg/g,0.1768mg/g,0.1356mg/g(n = 3),and the average extract yield was 39.0%(n = 3).Ethanol purification process:by using the orthogonal test,determinating Synephrine content,Verbascoside content of Ginsenoside Re,Rgl and Rbl content and extract yield,investigated liquid density,with alcohol content,alcohol precipitation time on the effect of alcohol precipitation.Thus optimized the best alcohol precipitation process:liquid relatively the density is 1.15g/mL(70?),containing 70%alcohol and alcohol precipitation 24h.The average levels of Synephrine,Mullein Glycoside,ginsenoside Re,Rgl and Rbl were 3.521mg/g,0.192mg/g,0.1679mg/g,0.1260mg/g(n = 3),and the average extract yield was 27.0%(n =3).Preparation molding process research:examine the impact of different materials and their quantities of granulation situation by comparing the test.As a result,mix raw herbs and accessories with the ratio of 1.6,wet extrusion granulation,drying below 80?,is injected into the volatile oil dissolved in 95%ethanol,sealed 24h,and finally aluminum packaging.2.Study on quality standardStudy on TLC qualitative:identify the 4 species of A,B,C,D in the Chinese herbal formula by TLC.Experimental results show that the product in reference substance chromatography corresponding control medicinal materials or position,all show the same colour spots,and the negative control in the corresponding position is no interference.And after the repeated experiments,the reproducibility is good.Study on content of HPLC determination:the preparations were determined by HPLC method of Synephrine content and Verbascoside content,with 18 alkyl slane bonding silica gel as the filling agent.The former mobile phase is methanol-0.1%potassium dihydrogen phosphate(50:50),velocity is 0.84mL/min,column temperature is 34?,detected wavelength 275nm.The latter mobile phase is acetonitrile-0.2%glacial acetic acid(13.2:86.8),velocity is 1.OmL/min,column temperature is 32?,detected wavelength 334nm.And the methodology,the results show that this investigation is rational and feasible,and good reproducibility,and can be used for the quality control of the Congzhikeli granules.The content of Synephrine is not less than 2.396mg in each bag.The content of Verbascoside is not less than 0.2207mg in each bag.3.Study on Medium-sized manufacturingThis part of the experiment investigated boiling alcohol precipitation process,the preparation process for industrial production,the indexes is yield,the synephrine transfer rate and the verbascoside transfer rate.The determination of the average finished product was 91.5%,average transfer rate of the Synephrine and the Verbascoside are 61.2%and 62.3%.The results showed that the preparation process of the Congzhikeli granules are basically suitable for the industrial production.4.Study on Preliminary stabilityStudy on preserving the samples at room temperature:the temperature is the natural temperature,humidity is 40-90%RH.Investigate the samples of traits,TLC,water content,solubility,Synephrine and Verbascoside content and microbiological limits in 1,2,3,6-month.Study on preserving the samples at high temperature and humidity:the temperature is 40?,humidity is 75%RH.Investigate the samples of traits,TLC,water content,solubility,Synephrine and Verbascoside content and microbiological limits in 1,2,3,6-month.