| Stroke,one of the four stubborn disease in traditional Chinese medicine-Feng/Lao/Gu/Ge,frequently happened in the elders,is now one of the three highest mortality rates human disease.460 million worldwide and 1.6 million people in China die from stroke each year respectively.Stroke,including ischemic stroke and hemorrhagic stroke,has a 6:1ratio between the two.And in ischemic stroke,there are transient ischemic attack(TIA),cerebral thrombosis and cerebral embolism.The latter two,difficult to distinguish clinically in sometimes,is referred to as cerebral infarction.In TCM,it is believed that the shortage of Qi is the pathogenic cause and XuePi is the is core of stroke.And recent studies have confirmed that blood stasis is the basic pathogenesis of cerebral infarction,so the basic principle is accelerating blood circulation in the treatment of infarction.The traditional view is that the application of Yiqihuoxue during the recovery stage is an appropriate treatment.Recent study found Yiqihuoxue effects in the acute phase and convalescence.According to the above methods of traditional Chinese medicine dialectical theory,this study make DanShen(promoting blood circulation),ChuanXiong(promoting blood circulation and Qi circulation),and Ginsengthe(supplementing Qi)work compatibly to play a double effect of promoting blood circulation and Qi circulation,so as to cure stroke starting from the etiology and pathogenesis.Objective:To do an exploratory research on the development of DanShen dropping pill curing cerebral infarction,and strive to combine the advantages of traditional Chinese medicine prescription with modern dosage form and formulation technology,and get prepared for the development of new drugs with market prospects.The study is divided into the following three parts:First part Process research of effective ingredient extraction.Refining ginseng alcohol extraction process on the determination of total ginseng saponins and purifying the ginseng alcohol extraction using macroporous resin purification method by orthogonal test.By orthogonal test,refining the extraction process of DanShen and ChuanXiong based on LithospermateB,DanShen ketone?A,and ferulic acid.Separation and purifying the active ingredients by ethyl acetate extraction and macroporous resin purification methods.Results:1.The optimum extraction process of Ginseng:Reflux extract three times,each 2 hours,with 80%ethanol 8 times the amount of Ginseng after crushing it,and concentrate the extraction under reduced pressure(60 ?,-0.08MPa)to 1g crude drug/1ml,centrifuge.Flow the supernatant with 1 column volume per hour(1BV/h)flow rate through D101 macroporous resin column(crude drug:resin column volume = 1:3,diameter:height ratio =1:7),after adsorption,first wash impurity with water 2BV/h,then desorption with 5/3 BV 75%ethanol 2BV.The desorption liquid was concentrated under reduced pressure(60 ?,-0.08MPa)to a relative density of 1.18?1.20(50 ?heat measure)to get a thick paste and set aside.2.The optimum extraction process of DanShen and Chuanxiong:Reflux extract three times,each 1 hours,with 85%ethanol 8 times the amount of DanShen and Chuanxiong,and concentrate the extraction under reduced pressure(60??-0.08MPa)to 1g crude drug/1ml.Extracte with an equal volume of ethyl acetate two times,each time 5min.With ethyl acetate,the extraction was concentrated under reduced pressure(60 ?,-0.08MPa)to the relative density of 1.18?1.20(50? hot measured)to get a thick paste and set aside.Shake off ethyl acetate of the remaining liquid after extraction,centrifuge,and flow the supernatant at a flow rate 1BV/h adsorption by D101 macroporous resin column(crude drug:resin column volume = 1:1.2,diameter:height= 1:7).After adsorption;wash impurity with water 1BV,then desorption with 1 BV 70%ethanol 2BV/h.The desorption liquid was concentrated under reduced pressure(60 ?,-0.08MPa)to a relative density of 1.18?1.20(50 ? heat measure)to get a thick paste and set aside.3.Mix the above three kinds of thick paste,dried under reduced pressure(60 ?,-0.08MPa)to get a dry paste,crush it and set aside.Second part Preparation process research of DanShen dropping pill curing cerebral infarction.This section first determines reasonable proportion of the matrix and condensation conditions based on the index of appearance quality by single factor experimental study.And choose the optimal process based on the indexes of a composite score of appearance quality,dissolution time and pill weight difference to evaluate the factors effecting the forming of dripping pills by orthogonal.Results:Preparation process of dropping pills identified as:added the extract powder and matrix by the 35:65 ratio to the molten matrix(monoglyceride:PEG400:PEG4000:PEG6000 = 2:5:55:3),mix,heat and melt at 65 ?,thermal insulate.Drop it with a 5cm dropping distance and 50?60 d/min drip rate into 100cs dimethicone dropwise,the cooling temperature(cooling gradient)is at 5 ??20 ?.Under this process,moldability of pill is good,pill weight difference is<6.0%,dissolution time is 5.6 minutes on average.The preparation process of dropping pills is reasonable,stable and viable.Third part Standard quality research of DanShen dropping pill curing cerebral infarction.The dropping pills acquired from this process meet the requirements of Appendix IK items of pills under the 2010 edition of "Chinese Pharmacopoeia".Qualitative identify the three herbs by TLC;control the content of dropping pills on indicators of acid B,ginsenosides Re,Rg1 content,thus providing the basis for the establishment of dropping pills quality standards;this experiment also preliminarily investigated the dissolution,acceleration and long-term stability of DanShen dropping pill curing cerebral infarction.The results show the dropping pills obtained in this experiment 90%dissolute in 30 min,with good stability,steady character,and disintegration time and ingredient content. |
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