Preclinical study of five new drugs of Dai medicine dengtaiye in China

With the support of key projects of Yunnan Natural Science Foundation, key new product development plan, western new drug action plan of Chinese Academy of Sciences, and support of Ministry of science and technology, Kunming Institute of Botany, Chinese Academy of Sciences and Yunnan Institute of medicine have completed all the preclinical research work of class 5 new drugs of dengtaiye after five years, and passed the on-site examination of Yunnan food and drug administration It was officially accepted by the State Food and drug administration Dai medicine dengtaiye "can clear away heat, remove phlegm and stop coughing It is used for coughing, expectoration, chronic bronchitis and pertussis caused by phlegm heat blocking lung." It is included in the drug standard of Yunnan Province (1974 Edition) and Chinese Pharmacopoeia (1977 Edition) At present, there are many problems in the domestic production and sales of dengtaiye preparation, such as large clinical dosage and unsatisfactory effect With the support of key projects of Yunnan Natural Science Foundation, key new product development plan, western new drug action plan of Chinese Academy of Sciences, and support of Ministry of science and technology, Kunming Institute of Botany, Chinese Academy of Sciences and Yunnan Institute of medicine have completed all the pre clinical research work of 5 kinds of new drugs of dengtaiye and passed the on-site assessment of Yunnan food and drug administration, It was officially accepted by the State Food and Drug Administration (acceptance No.: cxzl10000007, cxzl10000008) The project comprehensively studied the chemical components of each part of the lampstand tree, isolated and identified 85 compounds, including three novel skeleton alkaloids, which were listed as the hot off press by natural products reports in 2007, 2008 It was found that the monoterpene indole alkaloids were the main effective parts for relieving cough, asthma, expectoration, anti inflammation and analgesia, and Picrinine was the main effective substance The main pharmacodynamic experiments showed that dengtaiye alkali had a significant inhibitory effect on the lung adaptive strain (FM1, H1N1) of influenza A virus in vivo and in vitro It could significantly reduce the mortality and the degree of lung lesions of H1N1 inoculated mice, prolong their life cycle, and the minimum effective dose of inhibiting influenza virus was 12.5mg/kg The preliminary pharmacological mechanism study showed that: dengtaiye alkali and Picrinine can significantly inhibit the writhing pain and formaldehyde phase II pain response in mice induced by acetic acid, but not the hot plate pain and formaldehyde phase I pain, indicating that the analgesic mechanism is not related to the center, but related to the inhibition of peripheral inflammatory mediators; dengtaiye alkali and Picrinine on the adrenal index and vitamin of mice There was no significant effect on the content of biotin C PGE2 in the lavage fluid of carrageenan foot swelling and inflammations of air sacs significantly inhibited the production of no and MDA, increased the activity of SOD, suggesting that the anti-inflammatory effect was not related to the regulation of pituitary adrenaline axis, but related to the inhibition of the release of inflammatory transmitters Cox and 5-LOX It is suggested that the antiasthmatic effect of betaine and Picrinine may be related to the inhibition of extracellular calcium influx, intracellular calcium release and PKC signaling system There was no significant difference in the effect of betaine and Picrinine on the threshold of cough of the superior laryngeal nerve in cats, suggesting that antitussive therapy was mainly peripheral and had weak centrality The safety evaluation showed that LD50 of acute toxicity in mice by gavage was 2740 times of the clinical dosage, and the maximum tolerance was 1100 times of the clinical dosage There was no animal death in beagle dogs after oral administration of dengtaiye in 2000 times of the clinical dosage The results of general pharmacological experiments showed that there was no effect of betaine on nervous system, cardiovascular system and respiratory system of experimental animals The results of long-term toxicity test showed that beagle dogs and rats were continuously given dengtaiye alkali for 13 weeks, and the drug was stopped for 4 weeks, and all indexes were normal It is suggested that the safe dose range is less than 60 times of the clinical dosage The preclinical research of dengtaiye new drug has published 7 papers in SCI journals such as organic letters, 4 papers in domestic core journals, applied for 3 patents and authorized 1.