Dihydrocodeine The Annua Compound Compatibility Antimalarial Superiority And Its Mechanism Is Discussed

Of all the human afflictions, the greatest toll has been exacted by malaria . even today .malaria , which is caused by plasmodium, disables and kills more people than any other infections diseases. Every year it causes clinical illness in 300 million to 500 million people. 1.5 to 2.7 million of whom die. At present, some 90 countries or territories in the world are considered malarious.IWith almost half of them located in Africa, south of the Sahara. Although this number is considerably lower than in the mid-1950s when 140 countries or territories were designated malarious it nevertheless means that 36%(2,020 millions) of the world's total population is still exposed to malaria risks. 90% of malaria cases and deaths occur in Africa, mostly among growing children.As we know malaria poses special control problems due to the increasing population at risk from the disease, the difficulties in eradicating the mosquito vector in the tropics and the emergence and spread of parasite resistance to commonly used antimalarial drugs, such as chloroquine, mefloquine.The purpose of this studies is to search a new antimalarial combination of high effect, quick acting as well as safety and low-price, which can try to solve the global increasingly serious drug resistance at present, by ways of researching the dihydroartemisinin combinating.Firstly, an orthogonal test with 3 factors and 3 levels as L9(34) was conducted to assay the EDJO in rodent malaria. The result indicated that the ratio of dihydroartemisinin : naphthoquine : trimethoprim at 1 : 6 : 2 was proper. Based on this ratio, the EDso of the combination with its ingredients were determined both on plasmodium berghei K-173 strain and RC line. The synergistic coefficients were calculated for 0.31 and 0.18 respectively, which far less than 1, according to the standards of Berenbaum's methods. The results demonstrate that the combination has apparent synergistic actions notonly on sensitive strain but also on resistant line. The further experiments proved that trimethoprim act as synergistic agent. Studies on parasite clearance rate and "28-day curative test" as well as the effect against P. knowlesi in rhesus monkey, the results indicated that combination is superior to the main ingredient 棗 naphthoquine in terms of CTso , CDso in rodent malaria and cure rate in simian malaria. The resistant to the combination and naphthoquine were developed. Results proved that this combination can delay the resistance of the main ingredient, naphthoquine.According to the toxicity , the LDso of combination and its ingredients in mice were determined. Additive toxicity was evaluated on this combination, which was similar to Fansimef and lower to chloroquine .The effect of combination on the ultrastructure of erythrocytic stage of P. berghei ANKA strain was observed compared with its ingredients. The combination integrates all advantages of ingredients. Its effect is more prompt and stringer than its ingredients.On clinical investigation, the effect of combination is identical to dihdroartemisinin. But 1-day treatment of combination will more suitable for clinic to apply and extend this combination compared with 5-day treatment of dihydroartemisinm.Summing-up, the combination of dihydroartemisinin possesses advantages of quick acting, high effect, lower toxicity, short period of treatment, blocking the transmission and delaying the drug resistance. So it will exert affirmative and virtual effect on the control of malaria.