Study On The Modern Preparation Of Classical Prescription Er-Yi Decoction

Drinking cold drinks would cause cold pathogen damaging the spleen Yang,thus triggering diarrhea and dysentery,which easily occurs in hot summer.Currently,the first-line drug available to treat diarrhea in clinical are synthetic drugs,such as levofloxacin tablets.However,some patients do not respond to the first-line treatment even more seriously appearing side effects.Therefore,developing more safe and powerful anti-diarrhea and dysentery medicines for clinical therapy is urgently required.According to the"TaiPingHuiMinHeJiJuFang",the traditional Chinese formula“Er-Yi decoction”in the form of powdering and infusion has curative effect on the symptom and the only drawback is the inconvenience when used.The dried ginger,bitter almonds and licorice in the prescription of Er-Yi decoction are all fried products of sand,but the principle and technological parameters of sand frying are not yet clear.Thus,in order to develop Er-Yi decoction into a safe,effective and convenient modern preparation,this paper carried out research on the sand frying process of the herbal medicines in the prescription,the preparation process and quality standard of modern granules.The main contents of this paper are as follows:???Study on the processing technology of sand frying of three herb medicines in Er-Yi decoction.1.Study on the processing technology of sand-fried licoriceThe effect of sand-fried processing on the chemical composition of licorice was preliminarily studied via Ultra Performance Liquid Chromatography?UPLC?coupled with multivariate statistical analysis?Principal Component Analysis,PCA;Orthogonal Partial Least Squares Discriminant Analysis,OPLS-DA?.Then the orthogonal design was employed to optimize the processing technology of sand-fried licorice for the enhancement of anti-inflammatory activity.According to the UPLC-DAD fingerprints,there was no new peak in processed licorice compared to crude licorice.But 25chromatographic peaks among the 32 common peaks of processed licorice changed significantly compared to the crude licorice.The similar result was obtained from UPLC coupled with Principal Component Analysis?PCA?,20 samples of crude licorice?n=10?and sand-fried licorice?n=10?were distributed in two groups clearly in the score plot of PCA.What is more,through OPLS-DA analysis,22 chromatographic peaks with variable importance project?VIP?values greater than 1.0 were found,and 17compounds were identified by UPLC-MS/MS,which including 10 flavonoids and 7triterpenoids.Subsequently,taking sand fried time,temperature and the ratio of sand-powder as factors,using the 80%methanol extract rate and isoliquiritin which markedly increased in sand-fried licorice as indicators,an orthogonal design experiment was performed to determine the processed conditions for sand-fried licorice,and optimized as:sand frying time was 2 min,sand frying temperature was 230?,sand-drug ratio was 10:1.Further,the anti-inflammatory activity of 80%methanol extracts of crude and sand-fried licorice were tested by using xylene-induced auricle swelling in mice.Sand frying process is conducive to improve the anti-inflammatory activity of licorice.This study provides a simple and feasible sand frying process for licorice,which provides a basis for clinical application and modern preparations of sand-fried licorice.2.Study on the processing technology of sand-fried gingerFirstly,ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry?UPLC-Q-TOF-MS?was employed to study the chemical composition between dried ginger and sand-fried ginger,and the L₉?3⁴?orthogonal experiment design was further adopted.The frying process parameters of dried ginger were optimized based on sand frying time,temperature and sand-drug ratio.It was found that after ginger fried with sand,the content of chemical components decreased overall,the content of 6-shogaol increased significantly,and the relative peak area increased by 56.70%,confirming that 6-ginerol was dehydrated to form 6-shaogaol in dried ginger.Subsequently,the content of 6-ginerol and 6-shogaol,the appearance characteristics of processed products and water extract yield were chosen as evaluation indexes,and AHP-CRITIC mixed weighting method was employed to determine the weight coefficient.The process technology of sand-fried ginger was determined as:sand frying time was 6 min,sand frying temperature was 180°C,sand-drug ratio was20:1.The content of 6-ginerol and 6-shogaol in the prepared ginger was 5.88 mg/g and0.39 mg/g,respectively,water extract yield was 17.41%,and the characteristics of the sand-fried ginger meet the requirements of the Chinese Pharmacopoeia.This study provides a process technology of sand-fried ginger,and also provides a basis for the development of modern preparations for Er-Yi decoction.3.Study on the preparation process of sand-fried bitter almonds.Based on the evaluation of the extraction rate,the content of amygdalin and the toxicity limit of the Prussian blue method.AHP-CRITIC mixed weighting method was employed to determine the weight coefficient of the indexes.Set the frying temperature,time and sand-drug ratio,an orthogonal experiment L₉?3⁴?was designed to optimize the preparation process of sand-fried bitter almond.Finally,the preparation technology of sand fried bitter almond was optimized as:sand frying time was 2 min,temperature was 180°C,the sand-drug ratio was 10:1.The content of amygdalin in the sand-fried bitter almond was 4.81%,the toxicity limit analysis by Prussian blue method revealed that the toxicity was less,indicating that the preferred process of sand-fried bitter almonds not only preserves the efficacy of bitter almond,but also reduces the toxicity.This study provides a process for sand-fried bitter almond,and also provides a basis for the development of Er-Yi decoction.???Study on modern preparation technology of Er-Yi decoction granule1.Study on the extraction process of Er-Yi decoctionWater decoction extraction process was applied in this study.With the extraction time,times on extraction and liquid-medicine ratio as factors,an orthogonal experiment design L₉?3⁴?with three factors and three levels was performed.The weighted coefficient of amygdalin,6-ginerol,isoliquiritin and water extract yield were determined by AHP-CRITIC?analytic-hierarchy process-criteria importance through intercriteria correlation?mixed weight method,and the parameters of water extraction process were preferred.Finally,the extraction process of Er-Yi decoction was optimized as:extract three times with 8 times of the amount of water,and each time was 60 min.The verification test results showed that water dry extract yield was 17.52%,and the content of amygdalin,6-ginerol,liquiritin were 25.33 mg/g,0.63 mg/g,2.37mg/g,respectively.The results indicated that the preferred extraction process can effectively extract the functional components of the herbal medicines in the prescription,and the process is stable and feasible.2.Study on the formation process of Er-Yi decoction granulesGranules have become the main dosage form of modern medicines because they are easy to take and the active ingredients are easily absorbed.In order to develop Er-Yi decoction granules,the formation process of the dry extract powder was studied.Firstly,the type and usage of the excipients were preliminarily optimized through pre-test.Then,the amount of materials,the proportion of excipients and the concentration of methanol were taken as the factors to be investigated,molding rate,angle of repose,tapdensity,dissolution time,and hygroscopicity rate were chosen as indexes,the weight coefficient of the indexes were evaluated by CRITIC method,and the response surface experiments was used to optimized the parameters of formation process.Finally,the formation process of Er-Yi decoction granule was optimized as:the proportion of dextrin and lactose was 1.2:1,the proportion of excipient and extract powder was 2.1:1,and the concentration of ethanol was 80%.The prepared granules have uniform color,and the fluidity,molding rate and solubility all meet the requirements.???Study on quality standard of Er-Yi decoction granulesFrom the three aspects of TLC identification,content determination and inspection,the quality control of Er-Yi decoction granules was studied.The established conditions of thin layer chromatography can identify the dried ginger,cinnamon,licorice and bitter almond in Er-Yi decoction granules,and negative no interference;Based on the detection methods of amygdalin in bitter almond,6-ginerol in ginger,and glycyrrhizic acid in licorice in the Chinese Pharmacopoeia,the HPLC content determination methods of the above three ingredients in Er-Yi decoction granules were constructed,The content of 6-ginerol,amygdalin and glycyrrhizic acid in 3 batches of Er-Yi decoction granules were 0.047 mg/g,14.58 mg/g,0.34 mg/g,respectively.The three batches of Er-Yi decoction granules were tested for their solubility,water content and particle size distribution according to the requirements of the granules in the 2015edition of Chinese Pharmacopoeia,all of which met the requirements.In summary,based on the efficacy ingredients,prepared detoxification,etc.,the sand frying process of licorice,dried ginger and bitter almond in Er-Yi decoction was studied systematically.The verification experiment confirmed that the optimized sand frying process not only preserve the active ingredients of the herbal medicines,but also has certain detoxification effect.Secondly,based on the water extract yield and the content of functional ingredients such as amygdalin,6-ginerol and liquiritin,AHP-CRITIC mixed weighting method was employed to determine the weight coefficient of each index.Then,an orthogonal experiment L₉?3⁴?was designed based on the factors of extraction times,extraction time and liquid-medicine ratio to obtain the extraction process parameters.Finally,the Box-Behnken response surface experiment was applied to optimize the formation process of Er-Yi decoction granule,and the preparation process of the Er-Yi decoction granules was optimized is as follows:Weigh the herb medicines in the prescription proportion,the medicines were extract by water extraction process,extract three times with 8 times of the amount of water,and each time is 60min.Then,the water extract was concentrated to dryness under reduced pressure in vacuum,powdered.Subsequently,add 2.1 times the amount of extract powder as the auxiliary material composed of dextrin and lactose in a ratio of 1.2:1,granulated with80%ethanol,and sieved to obtain Er-Yi decoction granules.From the three aspects of qualitative identification,inspection and content determination,the quality standard of Er-Yi decoction granules was studied.The prepared granules comply with the regulations and requirements under the granules of the 2015 edition of the Chinese Pharmacopoeia.