Study On The Prescription Screening And Preparation Of Zhizizhi Decoction

Objective:The effects of different ratios of Gardenia jasminoides fruit?GJF?and Fermented Soybean?FS??ZZCD1-4,1:1,1:2,1:4,2:1,w/w?on the content of its constituents geniposide,genistein,total iridoid glycosides,total flavonoids,and on the behavioural and intracerebral monoamine neurotransmitters dopamine?DA?,5-hydroxytryptamine?5-HT?,5-hydroxyindoleacetic acid?5-HIAA?,and on the absorption of geniposide and genistein in the body were observed in the Zhi-zi-chi Decoction?ZZCD?to screen for the perfect compatibility ratio of ZZCD.Preparation of film-coated tablets and optimization of the optimally matched process for ZZCD.Methods:1.Prepared ZZCD1-4 by decoction.2.The content of geniposide was determined by high performance liquid chromatography?HPLC?,the content of genistein was determined by ultra performance liquid chromatography-tandem mass spectrometry?UPLC-MS/MS?,and the contents of total iridoid glycosides and total flavonoids was determined by ultraviolet and visible spectrophotometry?UV?.3.A depressed mouse model was established by intraperitoneal injection of LPS in combination with solitary condition.ZZCD1-4 and fluoxetine hydrochloride were administered by continuous gavage for 7 d,and LPS was administered intraperitoneally 0.5h after gavage on day 7,with a model control group and a normal control group in regular feeding.Detection of behavioral indicators such as sugar-water preference,changes in body weight and food intake,tail suspension experiments,forced swimming experiments.Plasma and hippocampal monoamine neurotransmitter levels in mice were determined by UPLC-MS/MS method.4.The pharmacokinetics of ZZCD1-4 in rats were investigated by gavage administration in rats.The rats were randomly divided into four groups,ZZCD1-4 was administered orally,and blood was taken from the orbital vein plexus at 0.25h,0.5h,1.0h,1.5h,2.0h,3.0h,4.0h,6.0h,12.0h,24.0h and 36.0h after gavage,and the content of gardenia glucoside and dye lignin was detected by UPLC-MS/MS method.Pharmacokinetic parameters and blood-drug concentration curves were obtained using DAS2.0 pharmacokinetic software,and statistical analysis was performed using SPSS24.0 software.5.One-factor investigation was used to optimize the parameters of wetting agent,lubricant and pressure of the press to determine the best preparation of film-coated tablets from ZZCD extract.6.Validation experiments on ZZCD film sheets were carried out by examining the appearance,content,weight differences and disintegration time.Results:1.Geniposide,genistein,total iridoid glycosides and total flavonoids showed good linearity in the range of 0.05¹?g·mL^-1,7¹2?g·mL^-1,20¹000 ng·mL^-11 and 125²50?g·mL^-1,respectively?R²>0.999 7?,and the RSD values of precision,reproducibility and stability experiments were below 2%,and the average recoveries were 97.98%,96.76%,98.66%and 98.17%,respectively.2.Compared with the normal control group,the mice in the model group showed a significant decrease in body weight,food intake,sugar and water consumption rate,and a significant increase in immobility time in the hanging tail experiment and forced swimming experiment?P<0.01?.Compared with model mice,ZZCD2 and ZZCD3 groups increased body weight and food intake in depressed mice?P<0.01?;ZZCD1,ZZCD2,ZZCD3 and ZZCD4 groups increased sugar water consumption in depressed mice?P<0.05,P<0.01,P<0.01,P<0.01?;ZZCD2 and ZZCD3 groups shortened the immobility time of depressed mice in hanging tail and forced swimming experiments?P<0.05,P<0.05,P<0.05,P<0.01?;ZZCD3 group significantly increased 5-HT and 5-HIAA content in hippocampus and plasma of mice?P<0.01?and ZZCD4 group significantly increased 5-HT and 5-HIAA content in hippocampus and plasma of depressed mice?P<0.05?.3.The detection modes of genistein and geniposide in rat plasma were positive ion mode and negative ion mode,respectively.Both geniposide and genistein showed good linearity in the range of 1⁵00 ng·mL^-1and 1¹00 ng·mL^-1?R²>0.9992?.The intra-day accuracy was 2.87%,6.52%,0.56%,6.79%,6.22%,1.44%for geniposide and genistein,respectively.The intra-day precisions was 8.32%,2.21%,0.72%and 1.59%,3.45%,0.51%for geniposide and genistein.The precision range is 96.37%¹06.70%.The recovery of extractions was 98.06±1.82%,97.40±1.80%,94.31±3.25%and 98.35±4.10%,95.71±5.92%,96.05±6.75%for geniposide and genistein.The affect of matrix of geniposide and genistein were 98.27±2.62%,95.58±1.47%,94.94±2.90%and 97.72±3.96%,89.35±10.59%,98.67±4.78%.4.Preparation process of ZZCD film coating tablet:ZZCD extract powder is mixed with starch in 1:2 ratio,70%ethanol is added,to make soft material,granulated by 14 mesh sieve,dry,whole granule is made by 12 mesh sieve,magnesium stearate and PVPP are added,mix,press,coat,coat and test.The weight difference,disintegration time limits and hardness of the three batches of film-coated tablets in the validation experiment were all in accordance with the regulations,and the average content of geniposide was 17.341mg·g^-1.Conclusion:From the study of the variation patterns of pharmacokinetic components and antidepressant effects in ZZCD1-4,it can be concluded that the ratio of GJF to FS is the best ratio for ZZCD when it is 1:4.The best preparation process of ZZCD film-coated tablets screened by single-factor investigation is reasonable and feasible,without adverse odor,and provides a reference for the subsequent research and clinical application of ZZCD antidepressant agents.