Preparation Process Optimization,Toxicity Test And Pharmacodynamic Studies Of Guanyuzhixiesan

Guanyuzhixiesan is a traditional Chinese medicine compound consisting of Chinese geranium,mantle,bitter bean grass,cumin,and licorice Chinese herbal medicine based on the basic theory of Chinese Veterinary Medicine.Among them,Valeriana officinale and Burnet have been used as a king drug,which has the effect of dampness and diarrhea,and bitterpea as a herbal drug.It has the effect of clearing heat and stopping diarrhea.The cumin and licorice are jointly used to make the spleen modulate and conditioning breath.The role of drugs can be heat dampness,spleen conditioning breath,and used to prevent livestock diseases of the gastrointestinal tract.In this paper,the toxicity and partial pharmacodynamic effects of Guanyuzhixiesan were studied,and the extraction process of this drug was optimized.Completed the materials for the application of new anti-diarrhea drugs for declaring diarrhea,and provided the basis and parameters for the safety of clinical drug use and production.（1）Thin-layer chromatography and high-performance liquid chromatography were used to identify and analyze the effective components and their contents of gallic acid and matrine in Guanyuzhixiesan.The Box-Behnken effect surface method was used,the extraction rate of the Guanyuzhixiesan,the gallic acid content and the matrine content were as the evaluation index,the optimum extraction process conditions for extraction of Guanyuzhixiesan were selected:water as solvent,extraction twice,extraction time A total of 3 h,the amount of water is 16 times that of herbs.（2）The LD₅₀ was not measured in the acute toxicity test,and the maximum tolerated dose test was performed on 10 mice at a dose of 90 g·kg^-1.All the mice were not poisoned.The phenomenon indicates that the maximum tolerated dose of Guanyuzhixiesan is 90 g·kg^-1.80 Wistar rats were randomly divided into 4 groups and were given doses of 60 g·kg^-1,30 g·kg^-1,and 15 g·kg^-1 daily for high,medium,and low doses of Guanyuzhixiesan,and the control group was given an equal volume of normal saline for 28 consecutive days.No rats died from poisoning during the period,and all rats showed no abnormal behavior.The weight change trend of rats in each administration group was the same as that of the control group.With no significant Differences in blood physiological parameters,blood biochemical indexes,and organ coefficients between the two groups and the control group.（P>0.05）,histopathological observations of heart,liver,spleen and other organs in each group showed no lesions.（3）Fifty Kunming mice were randomly divided into 5 groups.Each group was given a dose of 50.4 g·kg^-1,25.2 g·kg^-1,and 12.6 g·kg^-1 each day.The positive control group was given aspirin at a dose of 13 mg·kg^-1,the control group was given an equal volume of saline,after 3 days of continuous administration,20μL of xylene was applied to the right ear of the mouse,The left and right ear of mice were taken with a punch and weighed,found that the aspirin drug group and the high and medium doses of Guanyuzhixiesan could significantly reduce the ear swelling rate in mice（P<0.01）,The swelling inhibition rate between the high dose group and the aspirin group was not significantly different（P>0.05）.Another 40 Kunming mice were dosed according to the above-mentioned doses.The rats were intragastrically instilled with ink on the third day.All the intestinal tracts were dissected.The distance of advancement of the ink in the intestine and the total length of the intestine were observed and recorded,compared with the control group,the bowel propulsion rates in all groups were significantly reduced（P<0.05）.The optimum extraction process conditions for extraction of Guanyuzhixiesan were selected:water as solvent,extraction twice,extraction time A total of 3 h,the amount of water is 16 times that of herbs,and there is no toxic effect.It can significantly inhibit the swelling of the ear of mice caused by xylene and significantly reduce the bowel propulsion rate of normal mice.