Study On The Preparation Process,Pharmacodynamics And Pharmacokinetics Of Sweet Potato Extract Granule

Objective:The planting area and productivity of sweet potato in China are abundant,which ranks first in the world.As a functional root crop,sweet potato is rich in polysaccharides,proteins,minerals,vitamins,dietary fiber,sterols and other substances,and is considered as a potential functional food.Our previous study showed that the phytosterols form sweet potato had significant anti-breast cancer activity,and clarified the effective substances basis:Daucosterol（DAU）,Daucosterol Linolenate（DLA）,Daucosterol Linoleate（DL）and Daucosterol Palmitate（DP）.At present,the tuberous root of sweet potato is widely used as raw materials for starch and other foods production.However,sweet potato skin is treated as industrial wastes,which not only leads to the waste of a large number of functional components,but also causes some pollution to the environment from industrial wastes.Therefore,this research based on the early stage of the research,is planned to use sweet potato as raw material to extract active ingredients and develop Sweet Potato Extract Granule by varieties selection and preparation process study.Further research is intended to discuss its influence on a tumor-burdened mice mammary gland tumor growth,and to conduct an elementary pharmacokinetic study,acquiring the medicine generation characteristics of active ingredient in mice.Methods and Results:1.Screening sweet potato varieties based on the content of active ingredientsThe contents of DAU,DLA,DL and DP in meat and skin of 36 sweet potato varieties were systematically determined and analyzed,and the varieties with higher contents of the four active ingredients and their total contents were selected by cluster analysis.The results of content analysis showed that the four active ingredients and their total contents varied greatly among different varieties of sweet potato.The coefficient of variation in sweet potato meat ranged from 59.08%to 112.15%,and the coefficient of variation in sweet potato skin ranged from 16.72%to 60.12%.Cluster analysis was carried out on the contents of 4 active ingredients and their total contents.Five varieties with high content in sweet potato meat were screened out,which were S5,S6,S11,S13 and S31,respectively.Four varieties with higher content in sweet potato skin were screened out,namely S11,S20,S21 and S22.2.Study on preparation technology of Sweet Potato Extract Granule（1）Study on extraction technology of sweet potato active ingredients:sweet potato（S11）was used as raw materials,the diacolation method is adopted to extract active ingredients,on the basis of the results of single factor experiment,in the above four kinds of active components of total gain rate as the evaluation index,with ethanol concentration,powder particle size,dipping time and dosage of solvents to investigate factors,to L₉（³4）orthogonal experimental design to optimize sweet potato active ingredient extraction process.Finally,the optimal extraction process of sweet potato active ingredients was determined as follows:ethanol concentration of 75%,powder size of 30～40 mesh,immersion time of 30h,solvent dosage of 6 times.The process verification results showed that the average total extraction yield of the extract was 1.264%,showing the method was stable and feasible.（2）Study on the forming technology of Sweet Potato Extract Granule:preliminary screening of excipients was conducted,then the dextrin and lactose were selected as excipients finally.With the amounts of excipients,the proportion of excipients and the concentration of ethanol as the investigation factors,the molding rate,hygroabsorption rate,solubility,Angle of repose and pile density as the evaluation indexes,and the multi-index comprehensive score as the response value,the processing process of sweet potato extract granules was optimized by response surface analysis.Finally,the forming process of Sweet Potato Extract Granule was determined as follows:the ratio of dextrin to lactose was 0.59:1,the amounts of excipients were 1.54 times of the mass of dry extract powder,and the concentration of ethanol（wetting agent）was 70%.The results of process verification showed that the three batches of Sweet Potato Extract Granule met the requirements of each index,showing the method was stable and feasible.3.Effects of Sweet Potato Extract Granule on breast cancer tumor growth in tumor-xenograft nude miceMCF-7 breast cancer orthotopic tumor model was established to evaluate the effects of Sweet Potato Extract Granule on breast tumors in nude mice.Male BALB/c nude mice were randomly divided into 6 groups.They were normal control group（NC group）,tumor contolr group（TC group）,low-dose Sweet Potato Extract Granule group（SP-L group,0.75 g/kg）,medium-dose Sweet Potato Extract Granule group（SP-M group,1.5 g/kg）,high-dose Sweet Potato Extract Granule group（SP-H group,3 g/kg）,and positive drug group（CAP group,606 mg/kg）,respectively.The experiment lasted for 27 days.Tumor growth in nude mice was observed daily,and body weight and tumor volume were measured every 2 days.At the end of the trial,the nude mice were killed and dissected.The results showed that after 27 days of experiment,compared with the TC group,the average tumor volume and the average tumor weight in SP-H group were significantly decreased by 48.45%and 43.96%,respectively.Compared with NC group,there was no significant difference in the organ coefficients of mice in different doses of Sweet Potato Extract Granule.In addition,Sweet Potato Extract Granule can restore the weight loss caused by tumor development in nude mice to a certain degree.4.Preliminary study on pharmacokinetics of Sweet Potato Extract GranuleFirstly,a HPLC-ESI-MS/MS method for simultaneous determination of four active components in mouse plasma was established.The pharmacokinetics of the active components in ICR mice were studied by oral administration of sweet potato extract granules.The results showed that the established analytical method met the requirements in accuracy,precision,stability,linear range and specificity.The pharmacokinetic parameters were calculated by non-atrioventricular model after sweet potato extract granules were gavaged in mice.The results showed that DAU,DLA,DL,and DP were absorbed slowly in mice with half-time of 9.31,15.37,11.14,and 17.91 h,respectively.DL,DP,and DAU were more exposed compared with DLA,Average areas under the curve(AUC_0-24)were 7350,17960,17750 and 13390ng·h·m L^-1,respectively.Conclusion:To sum up,this study developed Sweet Potato Extract Granule with sweet potato as extraction materials through sweet potato variety screening and preparation technology research.It was found that Sweet Potato Extract Granule could inhibit the growth of breast tumors in tumor-xenograft mice and restore the weight loss caused by tumor development in nude mice to a certain degree.Preliminary pharmacokinetic studies showed that the four active components in Sweet Potato Extract Granule had similar pharmacokinetic characteristics in vivo:slow absorption and slow elimination.