| Sequelae of pelvic inflammatory disease[1-2]is a common clinical and frequently occurring disease,which is characterized by stubborn disease,repeated attacks,to bring great trouble to patients.The prescription of Shenpupenyan was proposed,combined the clinical practice of twenty years to the characteristics of sequelae of pelvic inflammatory disease by TAN Yong,who comes from Nanjing University of Chinese Medicine.The prescription is mainly used in the treatment of sequelae of pelvic inflammatory disease,with the function of clearing away heat and dampness and activating blood to resolve stasis.The prescription of Shenpupenyan is composes of ten herbals,such as Salvia miltiorrhiza Bge,Sargentodoxa cuneata and so on.By the daily dose,we know that this prescription takes a larger dose and not suitable for designing in tablet and capsule.The granules with small amount of additive material have the superiority of absorbing fast and rapid action,so we set the granules for target dosage.According to the Chinese traditional medicine and natural product medicine reporting requirement No.6.1 of Drug Registration Regulation of State Food and drug administration,fully complete the study on preparation process of intermediate,formation,pilot magnification,quality standards and stability,to ensure the safety,effectiveness,consistency of quality and stability of the medication in clinical.The main research connects are as follows.1 The preparation of Shenpupenyan granuleAccording to the results of literature research,the screening program of the intermediate system was formulated.Through the efficacy of screening,the intermediate process was selected,and the process parameters were optimized,the process of forming and the pilot scale study were studied.1.1 Extraction process route selection:Through consulting literature,combined with the physical and chemical properties of the active components,the preparation process of different intermediate systems was formulated and the main drug effects were selected.Will determine the giant knotweed rhizome and yanhusuo were extracted with ethanol and the remaining eight herbs using water extraction and alcohol precipitation.1.2 Study on the preparation process of the intermediate system:Taking the transport rate of tetrahydropalmatine,polydatin and dry extraction ratio as the index,study the technics of extraction for the medicinal materials extracted from ethanol in Shenpupenyan granule.Finally definite it as following:Polygonum cuspidatum was extracted for 3 times and 1.5 hours for each 10 times with 60%ethanol toghter with corydalis tuber,filtered,combined filtrate,standby.Taking the transport rate of peoniflorin and dry extraction ratio as the index,study the technics of extraction for the medicinal materials extracted from water in Shenpupenyan granule.Finally definite it as following:the medicinal materials extracted from water was extracted for 3 times and 1.5 hours for each 12 times with water,filtered,combined filtrate,and concentrated the filtrate to the relative density was 1.10(50?).Place the concentrated solution until the room temperature,then add 95%ethanol to 60%,standing 12 hours at room temperature,and taking ethanol supernate.Taking the transport rate of peoniflorin,tetrahydropalmatine,polydatin and dry extraction ratio as the index,to study the concentration and drying process of alcohol extract and alcohol precipitation supernatant in Shenpupenyan,and definite it as following:concentrated the mixed decoction to the relative density was 1.24(50?).Using the method of belt type vacuum drying(the three zone temperature is 100?,100?,90? and 30? for the cooling zone),the concentration of the solution was dried in two hours.1.3 Study on technics of formation:Taking the ratio of molding as the index,dextrin and stevioside as adjuvant material,to make granule for intermediate dry powder using dry granulation,and finally definite it as following:the ratio of powered extract,dextrin was 7:3?4:1 and stevioside dosage is 1%,the characteristics of granule compliance with the requirements of Pharmacopoeia,and the stability and homogeneity were good.1.4 The pilot study:according to the parameter optimization made by laboratory investigation,three batches of pilot scale test were carried out.The results showed that the preparation process is stable and feasible.2 Shenpupenyan granule quality standards researchTaking content determination and inspection items as evaluation indexes,initially established the quality standard of Shenpupenyan granule as following:established content determination method of peoniflorin and polydatin and TLC method for the identification of 5 herbs of Rhizoma Corydalis,radix salviae miltiorrhizae,Radix Linderae,and Polygonum cuneata.According to the relevant requirements of the 2010 edition of "Chinese Pharmacopoeia"General preparation in granules,we did research on the quality standard for Shenpupenyan granule including character,identification,dissolubility,moisture,granularity,load diference and content determination.Initially established the quality standard of Shenpupenyan granule as following:the product is brown granules;sweet,bitter;dissolubility,moisture,granularity,load diference and microbial limit compliance with the relative requirements of Pharmacopoeia,the content of peoniflorin and polydatin not less than 16 mg,9.3 mg per bag.3 Shenpupenyan granule of stability studyAccording to the preparation process to prepare three batches of Shenpupenyan granule,according to the product quality standard and related requirements of stability test of new drug of TCM,we respectively made the room temperature testing(the temperature is 25?±2?,the relative humidity is 60%±10%)and the accelerated stability testing(the temperature is 40?±2?,the relative humidity is 75%±5%).The results show that all indicators come up to the standards and quality is stable within 6 months of accelerated stability test and 18 months of long-term stability test.4 Study on the fingerprint of Shenpupenyan granuleFor the comprehensive control of the quality of Shenpupenyan granule,the fingerprints were studied for it and established the fingerprint analysis method.22 common peaks were demarcated and 9(the 9 components were gallic acid,sodium danshensu,chlorogenic acid,paeoniflorin,polydatin,benzoic acid,salvianolic acid B,emodin,physcion)of which were identified with reference.While the 22 peaks were belonged to corresponding herbs. |
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