Screening,Process Optimization,Pharmacodynamic Evaluation,Mechanism And Acute Toxicity Of Chinese Herbal Compound For Gout

Gout is a relatively common metabolic disorder associated with hyperuricemia and persistent elevation of urate in tissues,as well as with genetics,a high purine diet,the consumption of alcohol and sugary beverages.Hyperuricemia and recurrent acute gout are the clinical features of gout.Using western medicine to treat gout operates according to its developmental stage,while non-drug treatment is recommended for asymptomatic hyperuricemia,inflammation and relieve patients’pain.The inflammation and relieve patients’pain are reduced for the acute phase gout using colchicine or non-steroidal anti-inflammatory drugs.Reducing uric acid is essential for intermittent gout,commonly using drugs as febuxoat,allopurine and so on.The excretion of uric acid is needed for chronic phase gout using benzbromarone,prosulfa,etc.Western medicine treatment has many side effects and is prone to relapse,while Chinese medicine comprehensive treatment is efficient and safe.In this paper,Chinese medicinal materials commonly used in the treatment of gout and hyperuricemia were obtained based on a large number of literature research,and a new Chinese herbal compound for the treatment of gout was obtained through animal experiments screening,and its extraction and preparation process optimization,quality,pharmacodynamics,mechanism of action and acute toxicity were carried out in this study.First,two models of hyperuricemia in mice were replicated.In model 1,hypoxanthine was used to replicate the hyperuricemia model in mice,and the optimal dose was 250 mg/kg,in which positive drug was febuxoesta,and its dose was 3.3 mg/kg.In Model 2,uric acid was used to replicate the hyperuricemia model in mice,its optimal dose was 300 mg/kg,and the positive drug was benbromarone（20 mg/kg）.Secondly,the screening of Chinese medicinal materials for lowering uric acid.The hyperuricemia model of mice was replicated with hypoxanthine and used for screening the Chinese medicinal materials.The result showed that Terminalia chebula was found to be the best according to the ability of reducing blood uric acid.The effective part of Terminalia chebula was the ethyl acetate part with the best uric acid lowering,analgesic and anti-inflammatory effects.The acute toxicity study found that the LD₅₀of the hydrolyzed extract of Terminalia chebula was 33.73 g/kg,each dose group had little effect on the body weight of mice,and had some effect on the liver of mice,which was positively correlated with the dose,but had no significant effect on the indexes of other organs.The combination of Terminalia chebula and licorice could reduce the liver toxicity.In the screening and optimization experiment of Terminalia chebula compound,the best new compound was consisted of Chebula,Frankincense,Gentiana,Polygonatum,geranium and licorice of which its best ratio of Chebula:Frankincense:Gentiana:Polygonatum:geranium:glycyrrhiza=was 50:10:10:10:25:5,showed significant urico-lowering,analgesic and anti-inflammatory effects.The optimal extraction solvent was water extraction of frankincense,Gentiana,Polygonum cuspidatum,geranium and licorice together,and water extraction and acid hydrolysis and extraction of Terminalia chebula.Then,the optimization of the extraction process of Terminalia chebula and the process of compound granule preparation were carried out.Its optimal extraction process was obtained as follows:boiling reflux,extraction solvent was water,solid-liquid ratio was 1:14,extraction time was 1 h,extraction times was 3,acid hydrolysis concentration was 4 mol/L,acid hydrolysis time was 4.5 h,acid hydrolysis temperature was 99℃,p H before extraction was 2,extraction times was 3 and washing times was 0.The best preparation process of compound granules was obtained as follows:the best auxiliary material wasβ-cyclodextrin,the best dosage of auxiliary material was 25%,spray drying air inlet temperature was 170℃,liquid inlet speed was 400 m L/h,solution density was 1.10 g/cm³,adhesive type was 95%ethanol,drying time was 2 h.The best medicinal material of Terminalia chebula was obtained from Yulin,Guangxi.The quality control of Terminalia chebula was in line with the pharmacopoeia.The quality of compound granule conformed to the research standard.Finally,the pharmacodynamics of the new TCM compound was evaluated by using xylene induced ear swelling in mice,glacial acetic acid induced pain in mice,sodium urate crystal induced ankle swelling in mice,hypoxanthine or uric acid induced hyperuricemia in mice models.It was found that the medium dose（4.3990 g/kg）or high dose（8.7980 g/kg）of compound granules had significant effects on anti-inflammatory,analgesic,deswelling and lowering uric acid.It was found that the medium and high dose group of compound granules had significant effects on the liver of mice,and had certain effects on kidney protection,blood lipid reduction and spleen index.The preliminary study of the mechanism showed that compound granules significantly inhibited the activity of XOD in liver to reduce the blood uric acid and inhibit excretion in mice.The study of acute toxicity showed that LD₅₀of compound granules was 34.146 g/kg.When the confidence coefficient is a=0.05,the confidence interval of LD₅₀is 30.240 g/kg≤LD₅₀≤45.145 g/kg.The acute toxic symptoms were mainly death and idling.The body weight and organ index of mice were less affected by each dose group of compound granules.