The Studies On Screening,Extraction,Preparation Technology And Pharmacodynamics Of Traditional Chinese Medicine Compound For Gout Treatment

Gout is a kind of metabolic rheumatism,which is easy to relapse,but difficult to eradicate.Biochemically,it is mainly based on hyperuricemia,with main clinical manifestations of joint redness,swelling,fever and pain.Using chemistry medicine treatment,gout is treated mainly by analgesia,detumescence and reduction of uric acid,and its representative medications include non-steroidal anti-inflammatory drugs,glucocorticoids,allopurinol and benzbromarone.The medications are effective,but them mostly showed serious side effects,and discontinuance may often cause relapse.The side effects of Chinese herbal medicines are generally less in treatment of gout.In this paper,21 kinds of medicinal materials were selected according to existing literatures,as well as ancient books;then the best medicinal materials and compound combinations were screened out based on activities in inhibiting analgesia and detumescence,and reduction of uric acid;lastly,the extraction and formulation processes were improved,and its pharmacodynamic was evaluated.Firstly,three kinds of mouse models for pain,swelling and high uric acid were copied and used to screen the activities of 21 kinds of Chinese medicinal materials and their compound.The results found that the extract of single Clerodendranthus spicatus showed effective,and the compound extracts consisting of Cassia twig,Radix Paeoniae Rubra,Caulis Sinomenii,Achyranthes Bidentata,and Radix Glycyrrhizae also showed good activities in analgesia,detumescence,and uric acid reduction.Water and 70%ethanol were selected as the optimal extraction solvents for Clerodendranthus spicatus and compound combination,respectively;and the optimal ratio for compound was as follows:Cassia twig:Radix Paeoniae Rubra:Caulis sinomenii:Achyranthes bidentata:Radix glycyrrhizae=30:20:15:12:10.Then,the extraction processes for Clerodendranthus spicatus and the compound combination were investigated by comparing different extraction methods,different extraction ways and orthogonal design experiments and using target components and yield of dry extracts.The results showed that the optimal process for Clerodendranthus spicatus was:solvent(water),solvent and materials ratio(10:1),heating reflux temperature(80?),time(2 h),and times(2).For compound combination,Caulis sinomenii was extracted separately,while Cassia twig,Radix Paeoniae Rubra,Achyranthes bidentata and Radix glycyrrhizae were extracted together.The optimal process was:solvent(70%ethanol),solvent and materials ratio(12:1),heating reflux temperatue(60?),time(2 h),times(2).By above process,the content of target components and the yield of dry extract were relatively high.Lately,the formulation process was designed and optimized by single factor combined with orthogonal design,for Clerodendranthus spicatus granules,20%maltodextrin was used as the excipient,and the spray drying optimal process was:density of extract(1.05 g/cm~3),feeding speed(400 m L/h),and the air inlet temperature(180?);for compound granules,20%dextrin accounting was used as the excipient,and the spray drying optimal process was:density of extract(110g/cm~3),feeding speed(400 m L/h),and the air inlet temperature(160?).Under these conditions,the yield of dry powder was high,the water content was low,and the active ingredients were hardly destroyed.For granulation,a wet method was also used using 95%ethanol as the wetting agent and the granules prepared by above process showed good fluidity and uniformity.The physical properties and quality of granules were assayed according to relevant methods in 2015 edition of Chinese Pharmacopoeia,and the results showed that the qualitative components were identified by using TLC methods,quantitative components were determined by HPLC,particle size,water content and solubility met the requirements of Chinese Pharmacopoeia.The pharmacodynamical study was carried out by using mouse models with pain induced by glacial acetic,acute ear swelling induced by xylene,swelling for acute gout arthritis induced by MSU crystallization,and hypeluricemia induced by UA and HX.The results showed that the Clerodendranthus spicatus granules and compound granules could obviously inhibit effects on rat writhing induced by acetic acid,significantly improve the degree of xylene-induced ear swelling and MSU crystals-induced acute gouty arthritis toe swelling in mice.In addition,them could apparently reduce serum uric acid levels in hyperuric mice.This study laid a foundation for new drug study on granules of Traditional Chinese Medicine for the treatment of hyperuricemia or gout.