Transdermal Preparation Of Alkaloids From Seeds Of Strychnos Nux-vomica

Strychnos nux-vomica is a toxic traditional drug,which has significant analgesic and anti-inflammatory activity but narrow therapeutic window.Therefore,separation of the effective components and preparation of a long-acting drug delivery system have clinical significance.This dissertation consisted of four parts.In the first section,the development of extraction and isolation methods,pharmacological efficacy and toxicological effects of stiychnos alkaloids form seeds of strychnos nux-vomica have been reviewed,as well as the conventional and advanced drug delivery system.The second part focuses on establishing an efficient method for extraction and isolation of strychnos alkaloids.The optimum condition was as follows:ratio of solid to liquid was 1:10,ethanol concentration was 50%(pH=5),ultrasonic power was 600W,and the extraction time was 60min.The extraction rate of brucine was 9.94mg/g.The two-phase solvent system of HSCCC composed of n-hexane-ethyl acetate-methanol-water(3:5:3:5,v/v/v/v)was selected,brucine with the purity of 94.1%and strychnine with the purity of 92.5%were obtained.In the third part,the optimum formulation with orthogonal design of strychnos alkaloid gel paste was obtained as the follows,carbomer:sodium polyacrylate = 13:1,azone:propylene glycol = 1:1,the content of glycerol and strychnos alkaoilds were 40%and 20%respectively.The cumulative permeation curve of brucine through pig ear skin was consistent with Higuchi equation,the permeation rate was 491.05 ?g · cm-2 · h-1,and the 10h cumulative permeated percentage was 80%.The last part focuses on pharmacodynamics of strychnos alkaoilds and compound gel paste.After synoviocytes treated with 6.25 mg/mL,3.125mg/mL,1.5625mg/mL strychnos alkaloids for 24h,the morphological changes of apoptosis,such as cell rounding and shrinkage were observed.With arthritis index,toe swelling and pain threshold of CIA rats as index,the efficacy of high concentration group of compound gel paste was equal with high concentration group of positive control group.The above results revealed that transdermal preparation of strychnos alkaoilds shows favourable analegesic and anti-inflammatory activity,which was worth further developmental research.