Study On Preparation Technology And Quality Standard Of Jiayankangtai Granules

OBJECTIVE:Jiayan Kangtai granules are new compound preparations developed according to the requirements for the research and development of new traditional Chinese medicines and are clinical experience prescription.They are composed of Bupleuri Radix,Curcumae Radix,Prunellae Spica,Dioscoreae nipponicae Rhizoma,Fritillariae thunbergii Bulbus,Scrophulariae Radix,Cremastrae Pseudobulbus Pleiones Pseudobulbus,Astragali Radix,and Mume Fructus,treat Hashimoto's thyroiditis caused by liver qi stagnation and phlegm stasis.The purpose of this study is to screen the optimal preparation process of Jiayan Kangtai granules,establish the quality standards for the granules,and study their initial stability,then establish a HPLC fingerprint of granules,for the supplement of quality control.Methods:1.Extraction process study:The water extraction process and alcohol extraction process were investigated by orthogonal test method.The extraction rate and the proposed amount of Rosmarinic acid were used as indicators to inspect the water extraction process.The extraction rate and the amount of saikosaponin a,d proposed as indicators,inspect the alcohol extraction process of Bupleurum and other four herbs.Taking the extraction rate and the amount of Rosmarinic acid as indicators,the water extraction and alcohol precipitation process were investigated by the single factor method.2.Molding process research:Taking hygroscopicity,solubility,forming rate and fluidity etc as indexes to examine the best type of excipients(or ratio of excipients),and taking moldability as the index to examine the optimal amount of excipients and wetting agents(Ethanol)concentration;taking mouth feel as an indicator,the optimum amount of flavoring agent was examined.3.Quality Standards and Stability Study:Established the quality standards for Jiayan Kangtai granules.All the herbs were examined by thin-layer chromatography,and the qualitative identification methods of Bupleuri Radix,Prunellae Spica,Scrophulariae Radix,Fritillariae Thunbergii Bulbus,Astragali Radix five herbs were established.The HPLC method was used to establish the qualitative identification method.The method for determining the content of saikosaponin b1,b2 and rosmarinic acid in the preparation was established,and the content limit was established;the related inspection items under the granules were performed with reference to the relevant regulations of the 2015 edition of the Chinese Pharmacopoeia;and the stability was determined.4.Fingerprint study:The HPLC was used to establish the fingerprints of Jiayankangtai granules.Ten batches of the preparations were constructed based on the relative retention time of the common peaks and the RSD of the relative peak area to examine the precision,stability and reproducibility.Fingerprinting,calibration of common peaks,giving fingerprints of 10 batches of formulations similarity,and attribution of the source of the original medicinal material of the common peak.Results:1.Extraction process:The best water extraction and alcohol precipitation process for Prunellae spica and other three herbs is add 15 times amount of water,boiling 3 times for 2 hours each,and the extracts were combined and concentrated to a relative density of 1.00?.1.10(80?)or so,let cool,add ethanol to 70%alcohol precipitation,overnight,filter,and take the supernatant liquid to reserve;the best alcohol extraction technology of Bupleuri radix and other four herbs is add 6 times amount of 80%ethanol,extract three times,one hour per time,combine the alcohol solution,recover the ethanol,and combine with water extraction and concentrate the solution to the powder.2.Molding process:Take the dry paste powder obtained by the above extraction process,according to 1:1.5 add dextrin-lactose(3:1)auxiliary material and 1.0%aspartame flavoring agent,and mix well,use 80%ethanol as wetting agent,granulation.3.Established the quality standard of Jiayan Kangtai granules.Thin-layer chromatography was used to qualitatively identify the five-flavor herbs,such as Bupleuri radix and Prunellae spica,in the Jiayan Kangtai granules.The methods are accurate,convenient,reproducible,and specific;according to the "2015 edition of the Chinese Pharmacopoeia" General rules for preparations-granules were examined under the relevant provisions,moisture,melting,loading capacity differences,the results are in line with the provisions.The determination method of the content was established by HPLC.The granules contain Bupleuri radix calculated by the sum content of saikosaponin b1(C42H68O13)and saikosaponin b2(C42H68O13)should not be less than 0.5mg per bag,and contain Prunellae spica calculate by the content of rosmarinic acid(C18H16O8)should not be less than 1.4mg per bag;during the 6-month sample retention period of the granules,all important indicators did not change significantly,and the stability of the preparations was well.4.Established the HPLC fingerprint of Jiayan Kangtai granules,20 common peaks were marked,and 12 common peaks were identified.The sources of the raw medicinal materials were attributed;the precision,stability,and reproduction were used.The RSD of the relative retention time and relative peak area of 20 common peaks were all less than 5.0%,suggesting that the method is simple and reproducible;the similarity of the 10 batches of Jiayan Kangtai granules fingerprints is greater than 0.9.It is proved that the preparation process of this granules is stable and controllable.Conclusion:Through the inspection of the extraction process and molding process,the preparation process of Jiayan Kangtai granules suitable for pilot production was finally determined.Through the study of quality standards and stability studies,a stable and controllable formulation quality standard was established.Through fingerprinting research,the established fingerprint can be used as a new aid and complementary strategy for quality control.This study provides theoretical and technical support for clinical and industrialization.