The Preparation Of Gardeniae Flos And Aurantii Flos Capsules And Their Pharmacodynamics In The Treatment Of Sleep Disorder Alzheimer’s Disease

Objective:According to the strategic needs of developing the series of products of diet intervention for the aged with functional decline in"healthy aging",Jiangxi Daodi and its special resources,such as clearing liver and regulating qi,eliminating food,invigorating spleen,clearing lung and resolving phlegm,relieving depression,etc.,are selected to develop the Gardeniae Flos and Aurantii Flos of Jiangxi Daodi and special medicine and food resources.The brain aging,cognition,sleep and gastrointestinal tract caused by the common brain liver and spleen function decline in the elderly are selected The study of ad induced by isodysfunction has great clinical application prospect and therapeutic value of food therapy.The pharmacodynamic study of Gardeniae Flos and Aurantii Flos on sleep disorders Alzheimer’s disease with mild anxiety and depression was carried out.It was proved that Gardeniae Flos and Aurantii Flos have the pharmacological effect on the treatment of AD（sleep disorder,anxiety and depression）of sleep disorder Alzheimer’s disease（SDAD）.The preparation technology and quality of three capsule preparations of Gardeniae Flos and Aurantii Flos are completed at the same time,the basic research on the efficacy of three capsule preparations of Gardeniae Flos and Aurantii Flos on sleep disorders Alzheimer’s disease was carried out,which promoted the basic research results of Gardeniae Flos and Aurantii Flos to clinical application.The research results of this project will be beneficial to the comprehensive development and utilization of Jiangxi Daodi and characteristic medicinal materials,Citrus aurantium L.var.amara Engl and Gardenia jasminoides Ellis,will help farmers increase their income and get rich from poverty,and will promote the development of local economy in Jiangxi Province.Methods:1.According to the results of angle of repose and bulk density,the preparation technology of three capsule preparations of Gardeniae Flos and Aurantii Flos.Three crushing mesh numbers of Gardeniae Flos and Aurantii Flos were investigated by angle of repose,which were 65mesh,80 mesh and 100 mesh respectively,and the effects of the two amounts of magnesium stearate and silicon dioxide on the fluidity of the powder were also investigated.The type of capsule was determined by bulk density measurement.2.The microscopic characteristics of Gardeniae Flos and Aurantii Flos were studied through the identification and microscopic observation of the characters of Gardeniae Flos and Aurantii Flos;the qualitative identification of Gardeniae Flos and Aurantii Flos was carried out through thin-layer identification;the contents of methyl deacetylate,geniposide in Gardeniae Flos and naringin,naringin,hesperidin and neohesperidin in Aurantii Flos were determined by HPLC Research.The content of water,the difference of loading amount,disintegration time limit,extract,total ash,heavy metal and microbial limit of Gardeniae Flos and Aurantii Flos capsules were determined,and the quality standards of three capsule preparations of Gardeniae Flos and Aurantii Flos were established.3.The whole pharmacological model of sleep disorder Alzheimer’s disease（SDAD）with mild anxiety and depression symptoms was optimized.By measuring the learning and memory,spatial exploration,sleep disorder,anxiety,depression and other behavioral changes of SDAD model rats and detecting the physiological and biochemical indexes of brain,liver and spleen,it was confirmed that three capsule preparations of Gardeniae Flos and Aurantii Flos were effective in the treatment of SDAD Objective:To investigate the pharmacological effects on sleep disorders（sleep disorders,anxiety,depression）.4.Silica gel column chromatography,ODS-C₈ column chromatography,cyanide column chromatography,amino column chromatography and gel column chromatography were used for the column chromatography,and high performance liquid chromatography（HPLC）was used to separate and identify water-soluble constituents of macroporous resin and water soluble constituents from Gardeniae Flos and Aurantii Flos.The non-volatile components of Gardeniae Flos and Aurantii Flos capsules were identified and analyzed by UHPLC-Q-TOF-MS.The volatile components of Gardeniae Flos and Aurantii Flos capsules were analyzed and identified based on Agilent 7890 A/5975C gas chromatography-mass spectrometry.5.Accelerated stability test and long-term stability test were carried out,the stability of three capsule preparations of Gardeniae Flos and Aurantii Flos was studied.The key items were character,content,disintegration time and moisture.Results:1.The smaller the angle of repose,the better the fluidity.Through the determination of angle of repose,it was found that the angle of repose of 65 mesh Gardeniae Flos and Aurantii Flos pollen powder was smaller than that of 80 mesh and 100 mesh,and the fluidity was better.Therefore,the crushing particle size of the original medicine was determined to be 65 mesh.Through the determination of angle of repose,it is found that the angle of repose of the powder added with silica is smaller than that of the powder added with magnesium stearate,indicating that the fluidity of silica is better than that of magnesium stearate.Through the measurement of angle of repose,it is found that the angle of repose of 1.0%excipients is smaller than that of 0.5%excipients,so the dosage of excipients is 1.0%.According to the results of bulk density,No.0 hard capsule should be selected.In conclusion,the preparation process of Gardeniae Flos and Aurantii Flos capsules is as follows:65 mesh lyophilized medicinal materials with 1.0%silica,mix well,and fill No.0 hard capsule.2.The quality standards of three capsule preparations of Gardeniae Flos and Aurantii Flos were established:The capsule type is hard capsule,and the color of the capsule contents is yellow,yellow green and yellow brown.The results showed that the microscopic characteristics of Gardeniae Flos and Aurantii Flos were obvious,which met the requirements of microscopic identification;the TLC spots of Gardeniae Flos and Aurantii Flos were separated clearly,which met the requirements of identification;the samples all disintegrated within 30 minutes,which met the relevant requirements of disintegration time limit;the water content was less than 9.0%,which met the relevant requirements of capsule;the difference of dosage was within±10%,which met the relevant requirements of capsule;the detection of extract,total ash,heavy metal and microorganism met the relevant requirements of capsule.The content of index components in the content determination were in line with the relevant provisions of capsules,and the content determination methodology was in line with the relevant provisions of capsules.3.The results showed that the three capsule preparations of Gardeniae Flos and Aurantii Flos could shorten the latent period,increase the times of crossing the stage and prolong the time of staying in the fourth quadrant of rats with sleep disorder Alzheimer’s disease（SDAD）.The results showed that the three capsule preparations of Gardeniae Flos and Aurantii Flos could improve the learning and memory function,mental state and body weight of rats.The content of SOD increased,the content of ache and MDA decreased,the content of glutamate,NO and Ca²⁺decreased.It can effectively eliminate oxygen free radicals,improve the body’s anti-oxidation,anti-inflammatory and neuroprotective ability,so as to inhibit brain aging,soothe the liver,regulate qi and relieve depression（antidepressant）,slow down the decline of memory function,and improve sleep disorders and the anxiety caused by liver qi stagnation and tanyin symptoms Function.4.Through the separation and identification of water-soluble fraction,22 compounds were identified,mainly alkaloids,nucleic acids and amino acids.The non-volatile components of Gardeniae Flos and Aurantii Flos capsule were identified and analyzed by uhplc-q-tof-ms.the results showed that there were 36 compounds in Gardeniae Flos capsule and 43 compounds in Aurantii Flos capsule.Based on Agilent 7890 A/5975C GC-MS was used to identify and analyze the volatile components of Gardeniae Flos and Aurantii Flos capsule.The results showed that Gardeniae Flos capsule contained 28 volatile components and Aurantii Flos capsule contained 34volatile components,which were the quality control of three capsule preparations of Gardeniae Flos and Aurantii Flos and the disease model of Alzheimer’s disease（SDAD）with mild anxiety and anxiety Depression has laid a solid theoretical foundation.5.The results of accelerated test and long-term test showed that the indexes of three capsule preparations of Gardeniae Flos and Aurantii Flos were in line with the relevant provisions of capsules,indicating that three capsule preparations of Gardeniae Flos and Aurantii Flos were stable and suitable for industrial production.Conclusion:This project determined the preparation process of three capsule preparations of Gardeniae Flos and Aurantii Flos,including the preparation method of raw materials,the types of excipients,and the dosage of excipients,and prepared the finished capsules in line with the pilot scale specifications.This project carried out the identification of three capsule preparations of Gardeniae Flos and Aurantii Flos,the content determination of relevant index components,and the relevant inspection items,and established the relevant quality standards,which can provide reference for the development of three capsule preparations of Gardeniae Flos and Aurantii Flos.The results showed that the stability of three capsule preparations of Gardeniae Flos and Aurantii Flos was better.It is confirmed that three capsule preparations of Gardeniae Flos and Aurantii Flos have good functional efficacy in the treatment of sleep disorder Alzheimer’s disease with mild anxiety and depression.