Constituent Structure Of Antiviral Basis Of Radix Isatidis And The Modeling Technique Of Lanlian Minute Pellets

Radix Isatidis was recognized as one of the small number of traditional Chinese drugs that have anti-virus activity,but the research of Radix Isatidis was concentrating upon clinic and pharmaceutics,so the study of active component and material base was rather weak.According to available results,some support that Radix Isatidis have anti-virus activity,while others keep opposite point of this view.Through the research of the constituent structure of antiviral basis of Radix Isatidis,this study found that the antivirus activity of Radix Isatidis was the total alkaloids component with epigoitrin as the representation,Specific studies were as follows:1、Studies of the constituent structure of antiviral basis of Radix IsatidisCompared the anti-influenza A virus activity and anti-R.S.virus activity of Radix Isatidis extract from different origins through in vitro study,and used HPLC to determine the content of epigoitrin,2,4(1H,3H)-quinazolinedione,clemastanin B,and salicylic acid that were demonstrated have anti-virus activity directly or indirectly.Combined with in vitro study,we found that,epigoitrin have close correlation with anti-virus activity,which gave evidence to available literatures.Thereby,conclusion can be made that anti-virus activity of Radix Isatidis was mainly decided by the content of alkaloids like epigoitrin, phenyl propanoid content like clemastanin B have a synergism effect,antiendotoxin effect organic acids like salicylic acid and immunoloregulation effect of polysaccharides all make contribution to the integrate utility.2、Content comparison of representative components from the constituent structure of antiviral basis of Radix IsatidisConstructed a new HPLC method to determine epigoitrin and clemastanin B in Radix Isatidis from different origins,and improved the HPLC method to determine 2,4(1H,3H)-quinazolinedione and salicylic acid.By comparison,we found that the content of epigoitrin and clemastanin B of Radix Isatidis from hebei-anguo were maximum,and the content of 2,4(1H,3H)-quinazolinedione and salicylic acid were also relative high,so,it can be presumed that the quality of Radix Isatidis from hebei-anguo were better.3、Extract technology of the constituent structure of antiviral basis of Radix Isatidis and depurate technology of components groupThrough uni-factor test,the author found that water is the best menstruum to extract epigoitrin,but the content of epigoitrin extracted by water in 100℃is really seldom.By the comparison of the content change of epigoitrin control article and Radix Isatidis extract, the author detected that when the temperature was over 60℃,content of epigoitrin from Radix Isatidis extract decreased by about 30%(the decrease percent was different among Radix Isatidis from different origins),furthermore,content stoped decrease as the heating time went on,but it was unchanged of the epigoitrin control article,so the content reduction of epigoitrin may due to come possible reaction with other materials when the temperature was over 60℃.This study was finished by assistance with microwaves. Orthogonal experiment demonstrated the best extract technology:20BV water,60℃, 10min,and that can reach a extraction percentage of more than 92%.In addition, 2,4(1H,3H)-quinazolinedione can reach a extraction percentage of 87%,clemastanin B of 91%and salicylic acid of 71%through HPLC detection.Depurated alkaloidal components group,phenyl propanoid components group and organic acids components group were obtained from microwaves extract filtrate which is respectively adopted to 001×7(732#) strong acid cation exchange resins and HPD100 macropore polymeric adsorbent; polysaccharides components group was obtained from gruffs which were extracted by water and then settled by alcohol;content of total alkaloidal was measured by volumetric method,among the total is 28.52%,content of epigoitrin was 16.42%and 2,4(1H,3H)quinazolinedione was 2.78%;content of clmastanin B in phenyl propanoid components group was 2.98%;content of total organic acids was 19.16%,and among the total,content of salicylic acid was 1.27%;content of polysaccharides in polysaccharides components group measured ultraviolet and visible spectrophotometry by was 40.05%.4、Modeling technique of lanlian minute pelletsAdopting extrusion-spheronization process,applying spheral degree,flat critical angle, bulk density and yield of minute pellet as the index,the author investigated the drug-loading rate,secondary adjuvant and moistening agent through uni-factor test,result showed the best technology:drug-loading rate was 40%(the constituent structure components group of antiviral basis of Radix Isatidis and andrographolide),used microcrystalline cellulose as bailing accelerant(MCC,hold 50%in the formula),and usedα-lactose as secondary adjuvant(hold 10%in the formula),pellets prepared by this technology were spheral and the yield was high.Factors of extrusion speed,spheronization speed and spheronization time were investigated by L9(3~4) orthogonal experiment,when the extrusion speed was 30Hz,spheronization speed was 50Hz and spheronization time was 5min,satisfactory pellets were obtained.5、Studies of quality standard of lan-lian minute pelletsQuality control was the guarantee of curative effect of pharmaceutics in clinic. Employing HPLC,this study established approach to simultaneously determine epigoitrin and 2,4(1H,3H)-quinazolinedione in lan-lian minute pellets;established approach to determine clmastanin B in lan-lian minute pellets;and established approach to determine andrographolide in lan-lian minute pellets.The content of epigoitrin were respectively 7828.19、7825.84、7827.32μg/g in lan-lian minute pellets from three groups,the content of 2,4(1H,3H)-quinazolinedione were 1196.78、1199.55、1195.90μg/g,the content of clmastanin B were 1760.57、1761.30、1759.74μg/g and the content of andrographolide were 4436.92、4437.25、4435.16μg/g.In addition,powder technology and in vitro dissolution test were also investigated,result was satisfactory.If epigoitrin or 2,4(1H,3H)-quinazolinedione as the dissolution test’index,the minute pellets can dissolve 80%within 60 minutes.If andrographolide as the dissolution test’index,the minute pellets can dissolve 80%within 90 minutes.