The Study Of The Quality Control Material Basis And Standard Of Tongluoxingnao Effervescent Tablets

Tongluoxingnao effervescent tablets is an innovative compound medicine for traditional Chinese medicine,consisting of Ligusticum chuanxiong,Scutellariae Radix and Angelica sinensis three ingredients.This paper uses supercritical CO₂extraction technology and other extraction techniques to obtain the oil of Ligusticum chuanxiong,total flavonoids scutellaria,Angelica sinensis oil for medicinal material base,and uses the method of chemical evaluation to establish quality control indicators and evaluation methods for key links,meanwhile,carries out research on quality control of Tongluoxingnao effervescent tablets in order to ensure the quality stability and clinical safety of the finished product.The quality of Chinese patent medicine involves many key links.Raw medicinal materials used to produce finished products are the source of quality control.Due to the existence of multiple production areas and different processing methods in traditional Chinese medicines,quality instability often occurs.Therefore,it is necessary to control the material basis related to quality control for raw materials and the production.According to the characteristics of the tablets efficacy substance basis,in addition to the current regulations in the 2015 edition of the Chinese Pharmacopoeia,the study adds quality control indicators for volatile oil of Chuanxiong and establishes a limit standard that the content of the oil in Ligusticum chuanxiong is equal or greater than 0.50%.The quality control indicators for flavonoids is added to scutellaria,and the limit standard is set as the total flavonoid content of scutellaria must be equal or greater than 1.10%.The production and process conditions of Chinese patent medicine are the critical elements related to the limit of quality control indicators,and involved the transfer rate of the effective material basis in the production process,which will directly affect the strength and efficacy of the final product.The main effective substances of this product are volatile oil and flavonoids.Therefore,this study investigates the extraction process of Ligusticum chuanxiong,Scutellariae Radix and Angelica sinensis,and optimizes the extraction conditions for the volatile oil of Ligusticum chuanxiong as follows:40 smesh crushed,supercritical CO₂ fluid extraction,the extraction kettle 25 MPa pressure,extraction temperature 50℃,separation kettle Ⅰ pressure 7.5 MPa,temperature 47℃,Separation kettle Ⅱ pressure6.0 MPa,temperature 35℃,flow rate 38 L/h,extraction time 1 h.The extraction conditions for the Angelica sinensis oil is as follows:40 smesh crushed,supercritical CO₂ fluid extraction,the extraction kettle 30 MPa pressure,extraction temperature55℃,separation kettle Ⅰ pressure 7.5 MPa,temperature 47℃,Separation kettle Ⅱ pressure 6.0 MPa,temperature 35℃,flow rate 38 L/h,extraction time 1 h.The optimum extraction conditions of Ligusticum chuanxiong,Angelica sinensis and scutellaria are 60%ethanol,liquid ratio 1:8,extract 3 times,2 hours each time.The results show that this condition can better extract the main effective substances in the original medicinal materials.Because of the complexity of Chinese patent medicine and some of them are volatile and unstable,therefore,volatile substances need to be embedded in the production of pharmaceuticals to ensure stability during production and storage.To this end,this study uses modern inclusion technology to encapsulate oil of Ligusticum chuanxiong and Angelica sinensis oil,and investigates the inclusion conditions.the investigation results show that:the optimal inclusion technology for volatile oil of Ligusticum chuanxiong isβ-cyclodextrin:purified water（1:10）,dissolve at 60℃,β-CD and Ligusticum chuanxiong volatile oil quality ratio 5:1,closure time 2.0 h,Ligusticum chuanxiong volatile oil and anhydrous ethanol quality ratio 1:2,the crystallization time 1.5 h.After suction filtration,the inclusion compound was dried at40℃.for 4 hours.The optimum conditions for the inclusion of volatile oil in Angelica sinensis are determined as follows:β-cyclodextrin:purified water（1:10）,dissolved at 60℃,β-cyclodextrin:volatile oil of Angelica sinensis（6:1）,volatile oil:absolute ethanol（1:1）,closure time 2h,the crystallization time 1h.After suction filtration,the inclusion compound was dried at 40℃.for 4 hours.The results show that the embedding process is stable and reliable in quality.The quality control of Chinese patent medicine depends on various stages of the production process,especially the indicators and limit standards of the efficacy substances in each stage.For this reason,this study examines the key quality control indicators and limit standards for the three key steps of extraction of the product,embedding and shaping of volatile substances,adopts methods such as thin-layer chromatography（TLC）and high-performance liquid chromatography（HPLC）to select the indicators and methods of product quality control substances at all stages.The inclusion complexes of each of the volatile extracts of Ligusticum chuanxiong and Angelica sinensis,and the ferulic acid and ligustilide in the finished product are selected as the quality control indexes,and the content limit standards are also established.The baicalin,baicalein,wogonin and total flavonoids in extracts and products are used as quality control indicators,and formulated content limit standards.The results show that the quality control method established in each link is feasible;the quality standards formulated can ensure that the product is safe and effective.It provides scientific basis for the preparation of Tongluoxingnao effervescent tablets for clinical experimental study.