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1、Quinocetone IntroductionQuinocetone is 3-methyl-2-cinnimacyl-quinoxaline-1,4-dioxide in chemistry. The compound was selected and synthesized in 1983 by Lanzhou institute of animal and veterinary pharmaceutic sciences, CAAS. Quinocetone was named after its chemical structure, and was researched and d
2、eveloped as a novel animal drug and additive. Its research results were reported continuously. From 2000 on, quinocetone was further developed by both Lanzhou institute of animal and veterinary pharmaceutic sciences, CAAS, and China National Township Enterprises Corporation. Industrial productions o
3、f quinocetone and its premix were carried out in the end of 2003. The results of chemistry showed a great number of good conclusions. The structure of quinocetone was affirmed. Its materials were easily bought and synthetic procedure was few and easy. Production rate of quinocetone was high. Waste w
4、as little and was easily deal with. Quinocetone was fitted to production and its content was easy to determine.The results of pharmacology and clinic of quinocetone provide base for further study. Quinocetone was wide antibacterial range and inhibited many pathogen bacteria special to bacteria in tr
5、act. It can make incidence of diarrhea of poultry and livestock to low 50%70%. The best dosages of quinocetone to promote growth of chickens, pigs, fish were 75ppm, 50ppm and 75ppm，respectively. Similarly, the average increase rates in weight were 17.8%, 15.0% and 30.1%, and the average rate between
6、 food and meat in the end of experiment were more 11.8%, 9% and 17.7% than that in the beginning.Toxicology studies indicated that quinocetone was no toxicity. The LD50 of quinocetone in mice was 14398mg/kg. Quinocetone has no cumulatious effect in mices body. After adding quinocetone to feed with 5
7、0ppm, 75ppm, 100ppm, 150ppm, 300ppm for 90 days, biochemistry index in mice were normal. Five mice in each group were chosen to dissect and examine. Abnormity and toxic and side effect were not found. The NOEL(no observed effect level) of quinocetone in rats was 32.8(mg/kg bwd). Choosing the dose wh
8、ich was two to four times of approved dose to feed rats for twenty months continuously, there was no toxic and side effect, and the physiology and biochemistry index were also normal. Special toxicology and environment toxicology studies indicated that quinocetone had no special toxicity and environ
9、ment toxicity. The groups of quinocetone of 75ppm, 150ppm, 300ppm were the same to the blank control group. The appearance, internal organs and skeleton of live embryo mice and rats in three eras were not aberrated. There was no effect of inducing cancer in three dose additive groups. The mutation n
10、ature wasnt present whether quinocetone acted directly on TA98 and TA100 of mice typhus salmonella or after metabolize activation. There was no obvious increase caused by quinocetone on micronucleus rate of mices marrow. Sperm aberrance frequence was no obvious increase caused by quinocetone. Quinoc
11、etone can accelerate and improve propagate ability and foster survival rate. It also can increase avoirdupois and boost up immune function. Quinocetone had no harmful effects on plant and fishs growth, didnt pollute water environment, and has no toxic and side effect, so it can be used safely in fis
12、h-farming, which have certain effect in increasing survival rate and preventing fish diseases to extend live time.Quinocetone was excreted from urine in the original structure and its metabolite named 3-methyl-2-carboxyl-quinoxaline acid, which is cut side chain from original structure. Quinocetone
13、in animal was not long (chicken: T1/2K4.22h, pig: T1/2K4.73h). The metabolite of quinocetone eliminated very slowly in chicken and pig, because the elimination half time of its metabolites with mother structure was very long (chicken: T1/2K47.5h, pig: T1/2K113.5180.1h). The metabolite of quinocetone
14、 without mother structure eliminated quickly in chickens and pigs, because the elimination half time of them was close to its original structure (chicken: T1/2K4.04.2h, pig: T1/2K3.74.7h). After quinocetone label with tritium was given to chickens and pigs separately orally in fifteen and twenty mgk
15、g-1(13.6cimg-1) each time, the time of the radioactive excretion mostly in pigs urine is before three days, while that in pigs dung is before four days. The amount of excretion in urine is only about 10% of total of quinocetone and that in dung is not less than 70%. After quinocetone labeled with 14
16、C orally was given to chicken, more than 83% quinocetone was excreted from excrement and urine in 24 hours. The original structure of quinocetone remained not too long in animals edible organ (not more than 0 day). The metabolite of quinocetone with mother structure eliminated very slowly in edible organ of pigs and chickens (time of existence in chickens organ was not more than 0 day and that in pigs organ is not more than 21 days). The metabolite of quino
