| Scopolamine is a kind of tropane alkaloid with mydriatic,antispasmodic,anticholinergic,anesthesia,analgesic and sedative properties.The demand of scopolamine is great in worldwide.Hindu Datura is the main material for the preparation of natural chiral scopolamine,which is a medicinal plant distributed widely.However,the content of alkaloids in Hindu Datura is variable.If the current method of extraction and purification of scopolamine was applied to the raw materials with low content,the effect of separation and purification would be affected,because of its low extraction rate,low recovery and poor enrichment.Therefore,it is significative for the depth development of Hindu Datura to develop a novel preparation method of pure scopolamine(>99%)with high extraction rate,great enrichment and high recovery rate.In the present study,with the raw material of genuine Hindu Datura from the area of Northern Anhui,the process parameters of scopolamine extraction and separation from Hindu Datura were optimized.Firstly,the optical stability of pure scopolamine was studied.Then,the process parameters of extraction and separation were optimized and the affectois of improving the optical stability of scopolamine were applied in the process of extraction and separation,which could control the optical stability of target substance from the source.Through systematic research,the main results are as follows:(1)In the research of optical stability,according to the change of specific rotatory power in different p H,temperature and illumination,the experimental phenomenons were found as follows: scopolamine was relatively more stable in neutral and acidic conditions,which could produce a small amount of multirotation and degradation in the strong acid conditions,while the reaction of multirotation and degradation was performed quickly in the alkaline conditions and the degradation rate was accelerated with the increase of alkalinity;scopolamine was more stable in the low temperature environment and when the temperature was over 80℃,it would produce multirotation and degradation reaction rapidly;scopolamine was more stable under the condition of avoiding light and when the illumination increased,the scopolamine would gradually turn and degrade with the prolongation of storage time;scopolamine was more prone to change rotation at high concentration than at low concentration under the same condition.Therefore,in the preparation process of scopolamine,the conditions which have great influence on its optical activity should be avoided.In the storage process ofscopolamine,the way of storing in a brown bottle,cryopreservation and transforming into scopolamine salt can be applied to improve the optical stability of scopolamine.(2)In the research of extraction process,by comparing the conventional acid water extraction,the conventional ethanol extraction and ultrasonic-assisted extraction with dichloromethane,the ultrasonic-assisted extraction with dichloromethane was selected,because of its high extraction rate,simple process and convenient industrial production.Then the orthogonal method was used to optimize the process of ultrasonic-assisted extraction with dichloromethane,and the optimum extraction conditions of scopolamine were as follows: mass and volume ratio of raw material to ammonia water of 1:2,ultrasonic power of 180 W,ratio of material to liquid of 1:10,extraction temperature of25℃,extraction time of 30 min and extraction times of 2 times.Under this optimum condition,the yield of scopolamine was 0.091% and the content of scopolamine in the extract was 3.02%.Although a large number of ammonia was used in this step,it had been proved to have no significant effect on the opticity of final product.(3)In the research of separation and purification,a separation and purification method of scopolamine from Hindu Datura extracts was developed by combining liquid-liquid extraction,macroporous resins and crystallization,which had many advantages,such as less dosage of poisonous organic solvent,high purity and recovery rate,strong enrichment and purification effect,large amount of upper sample,simple and feasible process,and suitable for low content raw materials.The process of purification was as follows: firstly,the chloroform solution of crude extract was performed with liquid-liquid extraction including twice acid water in p H 6 and twice carbon tetrachloride in p H 7.5,and the content of scopolamine in the sample increased from 3.02% to 28.9%;secondly,the sample was purified by D151 resin in the condition of the loading volume of 10 bed volumes(BV),loading concentration of 0.191 mg/m L,p H value of 8,operation temperature of 25°C,flow rate at 2 BV/h,eluent(acid water)p H of 1,eluent volume of 16 BV and eluent flow rate at 2 BV/h,and the content of scopolamine in the purified sample was 83.1%;finally,scopolamine hydrobromide crystal was gotten after crystallization at-20°C overnight,and the content of scopolamine in the crystal was 99.12% and recovery rate was 77.45%.The rotatory stability was controlled by keeping p H and illumination in a certain range in the process and making the final product salt.Before use,we can reduce scopolamine hydrobromide to the scopolamine free state by alkali treatment.The product was characterized through optical activity,FT-IR,MS and 1H NMR.The results showed that the specific rotatorypower of the product was-24.9°,and the structure of the product was conforming to scopolamine hydrobromide. |
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