| Schisandra chinensis has high medicinal value and is the treasure of nature.It has the functions of enhancing body immunity,astringency and invigorating qi,protecting liver and liver,resisting cancer,delaying aging,regulating body function and promoting tissue regeneration.Schisandra chinensis has significant adjuvant therapeutic effects on liver diseases,cardiovascular diseases,central nervous system diseases and respiratory diseases.At present,Schisandra chinensis preparations on the market mainly include soft capsules,chewable tablets,granules and oral liquid.However,the low bioavailability of Schisandra chinensis components is a common phenomenon in existing Schisandra chinensis medicines and health products.The reason may be that Schisandra chinensis is insoluble in water and lignans can hardly be absorbed across the gastrointestinal biofilm in vivo.Self-microemulsifying drug delivery system is a new drug delivery technology developed by modern pharmacy in the field of nanometer.Dropping pills are traditional drug dosage forms.Combining the two,self-microemulsifying pills have the characteristics of high stability and low side effects,and also have the advantages of simple use and quick effect.Schisandrin self-microemulsion dripping pills are not only green and easy to manufacture,but also can increase the stability of drugs,improve the bioavailability of drugs in vivo,and promote the absorption and transportation of drugs in the gastrointestinal tract.OBJECTIVE:In this paper,through the development of schisandrin self-microemulsion dropping pills,we laid a foundation for the in-depth study of the gastrointestinal absorption mechanism of schisandrin in rats,opened up a new idea for the research and development of new dosage forms of schisandrin,and put forward a new basis for rational drug use and drug delivery program design.METHOD:1.To establish a method for the determination of lignans in Schisandra chinensis by high performance liquid chromatography in vivo and in vitro.2.According to the physicochemical properties of lignans in Schisandra chinensis and the hydrophilic-lipophilic equilibrium value of surfactants needed for the development of self-microemulsions,a large number of data were consulted.Firstly,several feasible oil phases,surfactants and cosurfactants were selected.The compatibility was observed,and the optimum SMEDDS formulation was determined by drawing ternary phase diagrams and Pseudoternary phase diagrams and evaluating particle size,drug loading and self-emulsifying time.The appearance characteristics,p H value,particle size,potential,morphology,drug loading and stability were investigated.3.Based on single factor conditions,the formulation and optimum preparation conditions of Schisandrin Self-microemulsion Dropping Pills can be determined by orthogonal experiment.The appearance characteristics,particle size,potential,morphology,content,stability and in vitro release were investigated.4.The pharmacokinetics of schisandrin self-microemulsion dropping pills in rats was studied by intragastric administration.Rats were randomly divided into three groups: group A was treated with Schisandrin Self-microemulsion Dropping Pills,group B with Schisandrin Self-microemulsion Dropping Pills + Verapamil Solution and group C with Schisandrin Self-microemulsion Dropping Pills + Isoniazid Solution.After 0.5h,1h,2h,3h,4h,5h,6h,8h,12 h,24h,the plasma,heart,liver,spleen,lung,kidney and brain tissues were taken respectively.After treatment,the lignans content of Schisandra chinensis was determined by HPLC.The pharmacokinetic parameters of Schisandra chinensis were calculated by DAS 3.0 software.RESULT: 1.The analytical results of Schisandrin A,Ester A and B by high performance liquid chromatography in vivo and in vitro are credible.2.The screened SMEDDS of schisandrin is schisandrin powder(9.10%),grape seed oil(9.10%),Tween 80(61.36%)and glycerol(20.44%).The self-emulsifying process of Schisandra chinensis lignans was completed within 3 minutes.The average particle size was 36.27±2.11 nm and zeta potential was-6.44±1.05 m V.The lignans were homogeneous and stable after centrifugation at high speed.The lignans were stable at room temperature for 6 months.3.The matrix,condensation matrix,temperature and dropping rate of dripping pills were selected by single factor investigation.After orthogonal experiment,the mass ratio of liquid to matrix,material temperature and dropping distance were determined.The optimum preparation method is: Schisandrin from microemulsion is mixed into pre-melted PEG 6000 at a mass ratio of 1:3 at 75?in water bath.After stirring,it is dripped into methyl silicone oil condensate at 2~10? at a speed of 40 drops/min at 15 cm.After cooling,it is taken out,methyl silicone oil on the surface is removed by ether,and the filter paper is dried.The milky white dropping pills were diluted 100 times,and the average particle size was 38.48±3.18 nm.The self-emulsifying time of zeta potential was-10.8m V was less than 4 minutes.Schisandrin from microemulsion dropping pills can be quickly dissolved in vitro,and the release rate is good.Dropping pills remained stable after 6 months of storage at room temperature.4.Data intelligent analysis was carried out by using DAS 3.0 pharmacokinetic analysis software.The best pharmacokinetic models of three lignans in Schisandra chinensis were two-compartment models.The results of pharmacokinetic study in rats showed that Schisandrin A did not change Tmax,Cmax increased significantly,Tmax of ester A and B remained unchanged and Cmax decreased slightly in schisandrin self-microemulsion dropping pills compared with rats given verapamil and isoniazid.CONCLUSION:1.The methods of schisandrae alcohol methyl ester methyl and ethyl in vitro and in vivo are reliable.2.The self-microemulsion formula showed that the self-microemulsion of pentastellanthin was O/W type,the particle size was 36.27 ±2.11 nm,the potential was-6.44±1.05 m V,and the stability was good.3.The results of dropping pills showed that the self-microemulsion dropping pills were round in appearance and uniform in size,with a particle size of 38.48±3.18 nm and a potential of-10.8±2.15 m V.4.The results showed that the pharmacokinetic model of schisandrae in rats was two-compartment.5.The kinesiology results of tissue traditional Chinese medicine showed that the concentration of alcohol a and b in liver and heart was higher and the retention time was longer,indicating that the self-microemulsion dropping pills prepared in this experiment were more beneficial to the treatment of liver and cardiovascular diseases.INNOVATION:1.A safe and reliable Schisandrin self-microemulsion dripping pill was prepared by using grape seed oil as oil phase.It has the characteristics of quick release,easy to carry,easy to take,and can cover up the taste.2.Schisandra chinensis lignan self-microemulsion dropping pills is a new preparation of Schisandra chinensis.It provides a new idea for the study of new dosage forms of oral absorption of insoluble drugs.3.The pharmacokinetics of the new formulation in rat plasma and tissues was studied.The pharmacokinetic parameters were obtained,which provided a new basis for rational drug use and drug delivery scheme design. |
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