| Xiaoer Chiqiao Qingre Granule consists of 14 Chinese herbal medicines such as forsythia,fried hazelnut,light soybean meal,artemisia annua,and mint,etc.It is now included in the 2015 edition of the Pharmacopoeia of the People's Republic of China(the following abbreviation as the "Chinese Pharmacopoeia").The proprietary Chinese medicine of the jichuan pharmaceutical industry group has a good clinical effect on the treatment of pediatric wind-heat flu syndrome.However,most Chinese medicines preparations have the following problems: 1.The quality standard is simple.2.The basis of pharmacodynamic substances is unclear.3.The clinical advantages and characteristics of the action are not clear.As the saying goes "medicine is good,medicine is good",the quality of Chinese medicines determines the quality of the final preparations,so the quality standard improvement from Chinese medicines to preparations can better control and improve the quality of the product.This subject is derived from the standardization construction of the national Chinese medicine standardization project-Xiaoer Chiqiao Qingre Granule.Our research group has undertaken the research on the quality standard improvement of Xiaoer Chiqiao Qingre Granule and Gardeniae Fructus.In the 2015 edition of the Chinese Pharmacopoeia,the quality standards for Xiaoer Chiqiao Qingre Granule include TLC qualitative identification of forsythia,rhubarb,red peony,schizonepeta and astragalus,and quantitative analysis of geniposide and forsythin.Qualitative identification and quantitative analysis of geniposide in Gardeniae Fructus.Because of the multi-component and multi-target characteristics of traditional Chinese medicine,only a single or a few indicator components used for qualitative and quantitative analysis can not fully reflect its quality and clinical efficacy,and can not meet the market demand.Therefore,it is necessary to carry out research on the quality standard improvement of Gardeniae Fructus and Xiaoer Chiqiao Qingre Granule.This paper firstly summarizes the research progress of Gardeniae Fructus and Xiaoer Chiqiao Qingre Granule.On the basis of the quality standard of Gardeniae Fructus and Xiaoer Chiqiao Qingre Granule in the 2015 edition of Chinese Pharmacopoeia,on the one hand,from TLC identification,HPLC fingerprint,multi-component content determination and water,ash,heavy metal and other inspection items,the quality standard of Gardeniae Fructus and firedGardeniae Fructus was improved;on the other hand,from TLC identification,HPLC fingerprint and multi-component content determination,the quality standard of Xiaoer Chiqiao Qingre Granule was improved.The research content is summarized as follows:1.Research on the improvement of quality standards of Gardeniae FructusBased on the quality standard of the 2015 edition of Chinese Pharmacopoeia,because the original standard is too simple to fully represent the quality of Gardeniae Fructus,it is necessary to carry out research on quality standards.(1)a multi-index TLC method for the identification of methyl acetyl chlorophyllin,genipin glucoside,geniposide and crocin I was established.The spots of each component were clear and well separated.This method is specific,accurate and effective.Through the study of 33 batches of Gardeniae Fructus from 11 different producing areas,the results showed that the quality difference of different producing areas was more obvious.(2)acetonitrile-0.1% phosphoric acid aqueous solution as the mobile phase,the detection wavelength was 238 nm and 440 nm,and the chromatographic elution was established by switching the wavelength.The methodological investigation met the requirements and 15 common peaks were determined,all batch similarity was above 0.90,SPSS cluster analysis and principal component analysis were carried out,and 33 batches of samples can be divided into 3categories.Further,by calculating the F comprehensive score,the results showed that there was still a difference in quality between different areas under the premise of similarity,and Anhui and Jiangxi were better.(3)Based on the chromatographic conditions of the HPLC fingerprint of Gardeniae Fructus,a HPLC method for the determination of five components of methyl acetyl chlorophyllin,genipin,crocin,crocetin I and crocin II was established.The methodological study met the requirements,and the content range of ingredients was 0.61~4.26 mg/g,1.73~12.92 mg/g,51.79~82.76 mg/g,5.03~12.80 mg/g,0.42~2.28 mg /g;the highest content of geniposide was its main component,and the content of genipin gentioside was more different than that of other components;(4)acid-insoluble ash and heavy metals were added on the basis of water and ash inspection items.And the limits were specified: acid insoluble ash should not exceed 0.2%;Cu ?20000 ng/g,As ? 2000 ng/g,Cd ? 300 ng/g,Hg ? 2000 ng/g,Pb ? 5000 ng/g.2.Research on the improvement of quality standards of fried Gardeniae FructusThrough comprehensive consideration of the yield,market and composition content and stability of Gardeniae Fructus,Jiangxi Gardeniae Fructus was selected as the source of fried Gardeniae Fructus in Xiaoer Chiqiao Qingre Granule.Because the Gardeniae Fructus in Xiaoer Chiqiao Qingre Granule is used as a medicine in the form of fried Gardeniae Fructus,it is necessary to carry out research on the quality standard of fried Gardeniae Fructus.We have collected 10 batches of fried Gardeniae Fructus from Fuzhou in Jiangxi Province,and based on the newly established quality standards of Gardeniae Fructus,its quality standard was improved.(1)a multi-index TLC method for the identification of methyl acetyl chlorophyllin,genipin glucoside,geniposide and crocin I was established.The spots of each component were clear and well separated.The method was specific,accurate and effective,the results showed that the quality of fried Gardeniae Fructus was stable between batches.(2)The method of HPLC fingerprinting of fried Gardeniae Fructus was established.The methodological investigation met the requirements,and 14 common peaks were determined.The similarity was greater than 0.99.The cluster analysis was mainly divided into 2 categories.The results showed that the overall quality was relatively stable.(3)HPLC method for determination of five components of fried Gardeniae Fructus was established,the content range of ingredients was 1.81~2.45 mg/g,7.86~11.08 mg/g,46.21~71.12mg/g,0.99~1.82 mg/g,0.11~0.21 mg/g.The content of geniposide was slightly larger than other components,and the content of other components was relatively stable.Because safflorin is a kind of pigment,it is easily decomposed by heat,so the content after processing was low.(4)On the basis of moisture and ash inspection items,acid-insoluble ash and heavy metals are also added.3.Research on the improvement of quality standards of Xiaoer Chiqiao Qingre GranuleBased on the quality standard of Xiaoer Chiqiao Qingre Granule in the 2015 edition of the Chinese Pharmacopoeia,Xiaoer Chiqiao Qingre Granule was studied for quality standard improvement.(1)Based on the TLC identification of Forsythia,Rhubarb,Nepeta,Peppermint and Radix Paeoniae,the TLC identifications of fried Gardeniae Fructus,Artemisia annua and areca nut were added.The results shown that the chromatogram of samples has the same color spot as the chromatogram of the reference substance or the reference drug,and the correspondingnegative control has no interference,the spot of the component was clearly separated,all the methods were specific,simple,accurate and effective.(2)acetonitrile-0.1% formic acid was used as mobile phase and detecting wavelengths were 240 nm,280 nm and 250 nm,the HPLC fingerprint of Xiaoer Chiqiao Qingre Granule was established by gradient elution for switching wavelengths.The methodological investigation met the requirements,20 common peaks were determined,and the sample similarity was above 0.90.The results of cluster analysis and principal component analysis were used to comprehensively analyze the results.20 batches of samples were clustered into three categories: the first category was S13,S14,and S15;the second type was S7 and S10;the remainder was category 3;Principal component analysis results were consistent with cluster analysis.Combined with the load map and principal component score map,it was found that the results of classification were caused by peaks 7(the paeoniflorin)and peak 20(glycyrrhizic acid).The results showed that except for the individual batch samples,the overall quality of the product was relatively stable.(3)Based on the HPLC fingerprint method of Xiaoer Chiqiao Qingre Granule,HPLC method was established for the determination of seven active constituents of geniposide,paeoniflorin,forsythiaside A,baicalin,forsythin,baicalin and glycyrrhizic acid.The contents range were geniposide was 4.03~5.97 mg/g,paeoniflorin was2.22~3.94 mg/g,forsythiaside A was 7.63~9.67 mg/g,baicalin was 5.00~10.08 mg/g,even Amygdalin was 1.10~1.61 mg/g,baicalin was 0.86~1.74 mg/g,glycyrrhizic acid was 1.61~2.81mg/g.The results showed that the content of geniposide and forsythin in all samples was better than that of the 2015 Chinese Pharmacopoeia standard,and the content of components in different batches was generally stable.The active ingredient contents of most sugar-free samples were more than sugar samples,which may be related to the sugar preparation process.Baicalin was the highest content component,and the content fluctuation was larger than the other components.Therefore,it is necessary to strengthen the management control of the quality of Astragalus membranaceus in the later stage,to ensure the stability and uniformity of the final product quality. |
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