Synthesis And Preliminary Evaluation On Toxicity, Pharmacology And Pharmacodynamic Of Arecoline

Arecoline is one of the most active componets of Areca-nut. Arecoline has a good effect on expelling parasites, improving movement of gastrointestinal Smooth Muscle and resisting pathogenic micro-organism. Arecoline obtained mainly through extraction from areca. But the content of Arecoline in the Areca-nut was low.and the resource of Areca-nut was insufficint.In addition the extraction ratio of traditional extraction method was low.So its' clinical application greatly limited by such reason.This experiment researched the technology of synthetic Arecoline,and then optimization and improvement.New technology adoption Nicotinic Acid after esterification generated methyllnicotinate, and then repass N-methylation generated N-methyl iodinated Methyllnicotinated ammonium salt and then reducted by liquefaction sodium borohydride produced Arecoline.which reacted with moderate hudromic acid and recrystallicazated by absolute ethyl generated hydrobromic acid Arecoline. New technology not only improved synthetic ratio but also made the synthetic product become more purification and easy converted to massive product. During the experiment. we found four elements affected the synthetic ratio.That was the concentration of ethanol,react temperature,react time and the quantity of reduction.For getting the optimal working condition and improved synthetic ratio.We employed orthogonal to design experiment,and extreme difference analysis method with method of analysis of variance to analysis the experiment result.Consequently we get the optimal working condition the concentration of ethanol(43%),react temperature (0℃～3℃),react time(10h) and the quantity of reduction(reduction/reactant=0.333).We application TLC to identificate synthetic sample and we found that there were two orange points on the TLC sheet,in addition we emploied numeral-melting point to measure its melting.The result show that the melting point was 168℃～170℃(data 169℃～171℃),so we preliminary assertion the thing we synthsis was Arecoline.and then we employ HPLC to test the content of hydrobromic acid Arecoline.The result show that hydrobromic acid Arecoline after recrystallization,its content can reach 98%.and then we identification its structure with IR,UV,HMNR,CMNR.The result show that the thing we synthesis was hydrobromic acid ArecolineAnd then we researched the acute toxicity of Arecoline and hydrobromic acid Arecoline on mice.Hydrobromic acid Arecoline LD₅₀ was 454.38mg/kgB.W,Confidence intervel for 422.26～488.95mg/kg.BW. Arecoline LD₅₀ was 174.71mg/kgB.W, Confidence intervel for 145.22～210.14mg/kg.BW. Next we researched its effecte on movement of stomach intestine. The results showed hydrobromic acid Arecoline can improve the movement of mice' small intestine,excite the smooth musle of rabbits' small intestine and strength the tension and amplitude of smooth musle of sguinea pigs' gastrointestinal.After that.we took hydrobromic acid Arecoline as main component and cranked it into appropriate doseage form, we resarched its pharmacodynamics Then we checked its helminthicide effect.we test 50 dogs feces.Only 9 dogs feces was checked out swarm egg and then we let the dogs take in drug by 2.5mg/kg.BW and found that the drug had an obviously effect on helminthicide.Except light diarrhea there was no other side effects.