Prescription Optimization Of Tongjingbao And Pharmaceutics Study On The Optimal Prescription Pellets

Tongjingbao granules are used to treat dysmenerrhed which were exploited by Jiangsu Provincial Academy of Chinese Medicine.The prescription was consisted of Angelica sinensis（Oliv.） Diels,Corydalis yanhusuo W.T.Wang（processing with vinegar）, Cinnamomum cassia Presl,Aucklandia lappa Decne.et al.Tongjingbao granules can warm meridians,disperse coldess,remove dampness,regulate Qi,resolve blood stasis and stop pain.However,the product is according to original technology of water exacting and ethanol precipitation,the dosage form,preparation technology and quality standard need to be improved.Furthermore,Tongjingbao granules have strong effect on resolving blood stasis,so menstrual blood volume of some women increased obviously.Therefore,this paper is for the purpose of its prescription optimization to reduce the side effects,and preparing Tongjingbao optimal prescription pellets to facilitate the clinical use.1.Optimization of Tongjingbao prescriptionOn the basis of theory of traditional Chinese medicine,4 dismantlements were composed,according to the different effectiveness of the traditional Chinese drug in Tongjingbao prescription.Pain models and bleeding time of mice tail,coagulation time of mice models were chose to select the optimal prescription.The results suggested that the optimal prescription including Angelica sinensis（Oliv.） Diels,Corydalis yanhusuo W.T. Wang（processing with vinegar）,Cinnamomum cassia Presl and Aucklandia lappa Decne. can take the place of the original prescription,it can hold the curative effects and reduce the secondary action.2.Study on the preparation technics of Tongjingbao optimal prescriptionAccording to the related literature and the prescription’s function and property of every medicine,extraction process was designed.Angelica sinensis（Oliv.） Diels contents essential oil,polycose and phenolic acid.So, firstly,the essential oil was extracted,then water extraction was used to polycose and phenolic acid.Polycose was purified by ethanol precipitation and phenolic acid by AB-8 resin.The essential oil of Cinnamomum cassia Presl and Aucklandia lappa Decne.was extracted and then used water exacting and ethanol precipitation.Corydalis yanhusuo W.T. Wang was extracted by ethanol and purified by AB-8 resin.The specific technology was as followed:â‘ Study on condition for extraction of essential oil:two different methods for the extraction of essential oil from Angelica sinensis（Oliv.） Diels,Cinnamomum cassia Presl and Aucklandia lappa Decne were compared,which were supercritical-CO₂ fluid（SFE-CO₂） and steam distillation（SD）.The ligustilide contents in Angelica sinensis（Oliv.） Diels were 1.12mg/g and 5.25mg/g extracted by SD and SFE-CO₂ separately.The contents of cinnamaldehyde in Cinnamomum cassia Presl and Aucklandia lappa Decne were 6.81mg/g and 19.62mg/g,costunolide were 0.09mg/g and 12.71mg/g,and dehydro-α-curcumene were 1.15mg/g and 3.52mg/g extracted by the above two extraction methods.The results suggested that SFE-CO₂ extraction has advantages.Screening different extraction of essential oil by pharmacodynamics index:the pharmacological activities of different volatile constituent extracted by SD and SFE-CO₂ were compared by dysmenorrhea model and spasmolysis model.The results showed that:compare to the Tongjingbao granules groups,the extraction of essential oil by SFE-CO₂ and SD groups hold the curative effects of relieving pain,from the effct of spasmolysis,the extraction of essential oil by SFE-CO₂ and SD groups were more satisfactory than Tongjingbao granules groups,and it had significant difference,it indicated that it is very necessary to optimizate the prescription and prescription technology of Tongjingbao.The results also showed that extraction of essential oil by SFE-CO₂ is more satisfactory on spasmolysis than by SD.Combined chemistry and pharmacodynamics indexes,the method is confirmed as SFE-CO₂ to extract the essential oil.The optimal extraction conditions of the essential oil from Angelica sinensis（Oliv.） Diels using supercritical fluid extraction were pressure 25 MPa,temperature 40℃,extraction time 2 hour,and 15 MPa,55℃and 3 hour for essential oil from Cinnamomum cassia Presl and Aucklandia lappa Decne.â‘¡Study on condition for extraction of water:The orthogonal design was carried out for the extraction of Angelica sinensis（Oliv.） Diels,ferulic acid and total extract as the indexes.The optimal conditions were as follows:10 times water,extracting twice and 1 hour per time.The orthogonal design was carried out for the extraction of Cinnamomum cassia Presl and Aucklandia lappa Decne.,cinnamic acid and total extract as the indexes. The optimal conditions were as follows:10 times water,soaking 30min,extracting twice and 1 hour per time.â‘¢Study on condition for extraction of Corydalis yanhusuo W.T.Wang: tetrahydropalmatione content and total extract yield were chosen as the evaluate indexes,the orthogonal design was carried out to study the extraction technics of Corydalis yanhusuo W. T.Wang.The best conditions were as follows:50%ethanol which is 6 times of the medicine amount,reflux extracting twice,2 hours per time.â‘£Rudiment purification of the optimal prescription:On the basis of optimization of the extraction technological parameter,we adopt preliminary purification study on every drug of the prescription.Polysaccharides from Angelica sinensis（Oliv.） Diels were purified by water exacting and ethanol precipitation,the Industrial Arts is:relative density of water extraction was concentrated to 1.4,adding ethanol to make alcohol content arrive 80 percent,filtration to get precipitation,adding water make the precipitation dissolve,relative density of filtrate was concentrated to1.3,adding ethanol to make alcohol content arrive 60 percent,filtration to get precipitation,make it dry and get polysaccharides;phenolic acid from Angelica sinensis（Oliv.） Diels was purified by AB-8 resin,recovered ethanol solution from ethanol supernate of polysaccharide,added to processed resin,eluted with distilled water to colorless,then eluted 8 times given column volumn with 30%ethanol,recovered ethanol and dried.Using the water extraction ethanol precipitation method to remove the impurities from Cinnamomum cassia Presl and Aucklandia lappa Decne.,to concentrate the solution of water-extraction to a relative density of 1.10（80℃）,and then precipitated by 80% concentration of alcohol,ethanol in the supernatant was reclaimed.To purify alkaloids from Corydalis yanhusuo W.T.Wang,with AB-8 macroporous resin,the concentrated extract was put in a treated AB-8 macroporous resin,the unbounded components were washed-out by sterile water,and then removed the waste water,the extraction was eluted by 90%ethanol of 3 folds column volume.Polysaccharides from Angelica sinensis（Oliv.） Diels were purified by water exacting and ethanol precipitation;Phenolic acid from Angelica sinensis（Oliv.） Diels was purified by AB-8 resin.Purification of Cinnamomum cassia Presl and Aucklandia lappa Decne.was water exacting and ethanol precipitation.Total alkaloids from Corydalis yanhusuo W.T. Wang was purified by AB-8 resin.To observe the different effect of purified extract and crude extract,female mouse dysmenorrhea model and bleeding time of mice tail experiments were employed.The results suggested that there was no significant difference,but purification can reduce the total extract and be good for moulding,so purification was carried out.3.Praeparatum modeling techniqueTongjingbao optimal prescription pellets were prepared by WM-300 type automatic bed coating granulation equipment.From the micromeritic properties and in vitro dissolution of pellets,results displayed that Tongjingbao optimal prescription pellets preparated by fluidization process had high drug-loading（86%）,good bulk density,small caesural corner,beautiful and quality controllable.The conent of tetrahydropalmatione and ferulic acid were determined in this paper.