Studies On Preparation And Pharmacodynamic Of The Optimal Total Alkaloids Of Strychnos Nux-vomica

As one of the traditional Chinese medicine, Strychnos nux-vomica L has the effects of analgetic and anti-inflammatory, and can be used for the treatment of rheumatoid arthritis,osteoarthritis,periarthritis humeroscapularis,lumber muscle strain,sprain, acute posterior ganglionitis,ect.In the present study,there are alkaloids, glucosides, terpenoid, organic acids and other components in Strychnos nux-vomica L. Alkaloids are the main bioactive and toxiferous chemicals,which taking up about 2～5%.As one of its main components, brucine also has great pharmaco-activity,but the other component, strychnine has little activity and great toxicity,so that the alkaloids which are removed of most strychnine are considered as the active ingredient. Due to the potential toxicity, its further generalization and application are held-back severiously. Therefore transdermal delivery system is strongly recommended for its extraordinary dosage form, which can make sure that its therapeutic effects will be shown, and at the same time, its toxicity degrades. So the paper make a study on the preparation process and pharmacodynamics of the optimal total alkaloids, including its preparation process, transdermal characteristic, main pharmacodynamics and toxicology, hoping that the results could establish the foundation for developing the transdermal preparation of the optimal total alkaloids.The total alkaloids were extracted by orthogonal array methods. Preparation technology was determined according to the experimental results:fifteen times ethanol (v/v) of 70% concentration for 3 times, each time for 0.5 h. The total alkaloids were dissolved with 50% ethanol,and the solution were decompression to 0.08 of the original volume. The concentrated liquid were centrifugated, and the supernatant solution was put aside overnight at 4℃followed by centrifugalization. The supernatant solution was drying, weighed accurately, and then the optimal total alkaloids were prepared. The results showed that strychnine and brucine accounted for 52.42% and 26.00% of total alkaloids respectively, but the percentage changed to 22.99% and 42.33% after preparation, so most of Strychnine was removed from total alkaloids, while the content of brucine was not reduced, which indicated that the process was reasonable.The results of investigation on the optimal total alkaloids, total alkaloid and brucine in vitro percutaneous absorption indicated that the permeation rate and accumulated permeation percent of brucine solution is 5.71μg/cm2/h and(59.41±2.90)%,in the optimal total alkaloids with brucine is 6.41μg/cm2/h and(67.95±6.51)%, and in total alkaloids with brucine is 9.11μg/cm2/h and (73.52±11.22)%. In mixed solution, the permeation rate and accumulated permeation percent of strychnine had no significant difference. The results indicated that strychnine can encourage the rate and degree of transdermal absorption of brucine in total alkaloids.The paper made a comparison between the total alkaloids and the optimal total alkaloids in pharmacodynamic action after transdermal administration. The anti-inflammatory experiment induced by xylene indicated that the optimal total alkaloids can inhibit swelling of ear in mice, the curative dose of anti-inflammatory was 6 mg/kg, but total alkaloids had no effect at this dosage. The paper used DTH to investigate the immunologic function of mice by giving the two alkaloids. The result showed that compared with the control group, the optimal total alkaloids had significant difference at high-dose group (p<0.01),but others made no difference. Furthermore the optimal total alkaloids didn't impact the ponderal index of immune organ. The experiment indicted that the optimal total alkaloids had immunosuppressive action, but didn't influence the weight of immune organ. The analgesic effect was studied by adoption of ache model caused by acetic acid in mice and hot-plate test. The result showed that the optimal total alkaloids had analgesic effect, and its curative dose of analgesic effect was 12 mg/kg, while total alkaloids had no effect at this dosage.This paper compared two kinds of alkaloids in vitro anti-tumor activity of the evaluation and selection. The results showed that the optimal total alkaloids showed stronger inhibitory effects against a variety of tumor cells proliferation than total alkaloids, the effect showed a dose-dependent relationship. A2780 and LoVo cells were the most sensitive ones to the optimal total alkaloids, with growth inhibitory rates all above 80%.At the same time, acute toxicity test was used to determine the median lethal dose (LD50) of the total alkaloid and the optimal total alkaloids. The results showed that LD50 of the total alkaloid and the optimal total alkaloids were 6.400 mg/kg and 12.303 mg/kg, respectively. The optimal total alkaloids could reduce the toxicity to half of the total alkaloid.