The Research On Synergism And Attenuation Of The Novel Niuhuang Jiedu Tablets

Niuhuang Jiedu Tablet is a classical traditional prescription and the main function of the drug is detoxification.It can be used for ulcer of mouth and tongue swelling and pain of eye,gum line caused by inflammation.It is widely used in clinical practicets for its significant therapeutic effect and the cheap price.But this compound contains a lot of realgar which causes adverse reaction after long-term administration,and the clinical performances are symptoms of arsenic poisoning,allergies,skin lesions and gastrointestinal injury.The major problems to be solved in this paper is reducing the toxicity of Niuhuang Jiedu Tablet on the promise of reserving the therapeutic effect of the drug.We prepared realgar translation solution（RTS）taking microbial leaching technique based on the preliminary studies of our laboratory and the realgar in Niuhuang Jiedu Tablet was replaced by RTS.Then we explored the attenuation and synergy effects of the novel Niuhuang Jiedu Tablet through experiments.First of all we obtained the realgar bioleaching solution（RTS）by the methods of Chinese invention patent CN1853651 Pharmaceutical compositions containing cinnabar and/or realgar.Based on the preparation method of Niuhuang Jiedu Tablet in the Chinese pharmacopoeiawe,we obtained the novel Niuhuang Jiedu Tablet and RTS was used to replace the realgar in Niuhuang Jiedu Tablet.The arsenic content of the novel Niuhuang Jiedu Tablet is 1/1000,1/500,1/250,1/125 equivalent to the total arsenic content of Niuhuang Jiedu Tablets.In order to elucidate the attenuation and synergy effects of the novel Niuhuang Jiedu Tablet,the acute toxicity and 14 days toxicity experiment was done.The results showed that the median lethal dose(LD₅₀)of the novel Niuhuang Jiedu Tablets is LD₅₀>12.5g/kg.Then we calculated the maximum tolerance dose（MTD）of the drug according to the method of Chinese Medicine Pharmacology Research Methodology and the MTD is 180 times and it is greater than the safety multiples of 100 times.Pathological examination after 14 days toxicity experiment showed that the pathological damage of the liver and kidney in 1/1000,1/500 RTS alternative group was significantly lower than that in the positive group.This paper also studies the therapeutic effect of the novel Niuhuang Jiedu Tablet.The anti-inflammatory experiments indicated that the novel Niuhuang Jiedu Tablets could eliminate swelling effectively,but it did not show better effect than the positive group.The analgesic experiments showed that the novel Niuhuang Jiedu Tablets has a better analgesic effect compared with positive group.Antifebrile experiment showed that the 1/500,1/125 RTS alternative group had a better antifebrile effect compared with positive group.Antibacterial test indicated that compared with positive drug of Niuhuang Jiedu Tablet,the novel Niuhuang Jiedu Tablets had better antibacterial effects on Candida albicans,but it did not have better effects on Escherichia coli,Staphylococcus aureus,Pseudomonas aeruginosa and Bacillus subtilis.Finally,this paper studied cytotoxicity of the novel Niuhuang Jiedu Tablets on mononuclear macrophage cell line RAW264.7.And we also studied the effects of the novel Niuhuang Jiedu Tablets on the production of inflammatory factor NO and TNF-α.The results indicated that compared with positive group the novel Niuhuang Jiedu Tablets had lower cytotoxicity and could significantly reduce the production of inflammatory factor NO and TNF-α,and it is superior than Niuhuang Jiedu Tablets in a certain amount of alternative RTS range.In conclusion in a certain amount of RTS alternative range,the novel Niuhuang Jiedu Tablets has better antipyretic and analgesic effects,analogous anti-inflammatory effects and less toxic compared with Niuhuang Jiedu Tablets.The novel Niuhuang Jiedu Tablets have the efficacy of synergism and attenuation.