| Objective: The project according to the Chinese medicine theory and practice guidance,pharmacy,analytical chemistry,TCM chemistry,pharmacology,pharmacokinetics and modern analytical techniques combined,is a combination of study of traditional Chinese medicine and modern methods to make meaningful to explore.Through the study of high temperature,high humidity and light experiment of influence factors.The effects of Weitengning capsules in temperature,humidity,light under the influence of changes with time changes,drug production,packaging,storage and transportation conditions provide scientific basis,through the accelerated stability test under the condition of constant temperature and constant humidity storage at room temperature under the condition of long-term experimental test for stomach pain capsule Stability studies,establishment of Weitengning capsules reasonable validity.Through the Pinostrobin hormone metabolism research,clear the Pinostrobin in in vivo metabolism of concentration distribution,the metabolites of analysis and identification,presumably Pinostrobin in vivo occurred metabolic reaction pathways,for next step Weitengning capsules in metabolic studies provide the basis.Methods: Through the experiment of influence factors(high temperature,high humidity,light),accelerated test(temperature and humidity),long-term experiment(at room temperature)three experimental group,according to?Chinese Pharmacopoeia?2010 version of the second part of the appendix XIXC drug substances and to test the stability of preparation guidelines and Appendix I glue capsule inspection,combined with our laboratory previous preliminary formulation of Weitengning capsules and the quality standard draft,stability of Weitengning capsules.Influencing factors test is the weitengnin capsules were placed in the high temperature of 60?,high humidity 75%,under the condition of light 4500 lx ± 500 lx.On day 0,5 days,10 days to remove the amount Samples;accelerated test is at 40?,humidity of 75% under constant temperature and humidity conditions,at the end of the 0,1,2,3,6 respectively out appropriate amount of the sample;long-term experiment is under room temperatureconditions,according to the commercially available packaging stored.At the end of the 0,3,6,9,12 were removed the right amount of samples.In preliminary laboratory on the basis of the study,samples will be taken out according to stability key investigation project(characteristics,water content and amount of difference,disintegration time,TLC,microbial limit test,effective component content and fingerprint chromatogram similarity)were detected.The UPLC-MS research analysis of the Pinostrobin in the positive ion mode of Characteristic fragmentation patterns,the establishment of measuring Pinostrobin UPLC-MS analysis method.On rat irrigation stomach stomach the capsule of the index component ball pinocembrin by UPLC-UV and UPLC-MS / MS techniques,of rats after intragastric administration of plasma,urine,feces and bile and including the heart,liver,spleen,lung,kidney,stomach,large intestine,small intestine tissue were qualitative and quantitative analysis,explore the Pinostrobin in distribution and metabolism of rat in vivo metabolites and metabolic pathways.Results:(1)Weitengning capsules in three experiments,the high temperature of60?in 5 and 10 days of capsule shell will harden and high humidity 75%10 day capsule shells,will become soft,light under the condition of capsule shell without significant changes,other items are in line with the requirements.Accelerated test after 3 months appear soft capsule shell;long-term experiment in December appeared a very small amount of capsule shell to harden.(2)5 rats a single intragastric administration Prill pinocembrin,build up the Pinostrobin the plasma concentration-time curve,according to the average pharmacokinetic parameters,maximum plasma concentration was Cmax=45.51 ± 19.33(ng / ml),the maximum concentration(i.e.up to the peak time)Tmax=12.4 ±9.84(min)elimination phase of half-life t1/2=221.64±139.52(min),detected in the excrement in the Pinostrobin prototype,urine when administered 4 h with the peak excretion,fecal samples is at 12 h after 24 h peak excretion and bile metabolism is at 0h to 7h excretion rapidly.Rats were gavaged with the Pinostrobin)After the Pinostrobin in different time and different tissue distribution of the change,distributed in the stomach content was the highest,followed by the small intestine,again for Escherichia,liver,kidney,heart,lung and spleen.From rat gavage in the plasma and urine after administration to found the prototype M0 and 10 kinds of metabolites.The M1 may for the Pinostrobin element in isomerase occurrence of heterogeneous reaction to obtain the ball pinocembrin check chalcone,M2 is Pinostrobin to methylation products,pinocembrin,M6 as pine plain hydroxylation reaction product.Conclusion: Stability test results show that the experiment of influence factors,accelerated test and long-term experiments of capsule shell can produce effect,make it become soft or hard,and content had no obvious change.Through the analysis of experimental factors affecting the experimental results,the stomach capsule in storage and transportation process should avoid high temperature and high humidity and to open the capsule packaging especially to do moistureproof processing.Through accelerated testing and long-term experiments on the existing results,calculate the weitengnin capsule is valid for one year.Under the provisions of the need to continue to test the long-term experiment 18 months,24 months,36 months of data.Diversification of one component of a major role in loose loose ball of Chinese patent medicine by plasma kinetic parameters indicated that the Pinostrobin in rats in vivo metabolic accorded with two compartment open model.Excretion data display,urine,feces and bile total excretion is very low,so the Pinostrobin grain is mainly in vivo transformation and metabolism.The project research of Weitengning capsules is treating gastropathy,which content is higher in tissue sample analysis results,in the stomach and small intestine of the highest distribution.The experimental results also show that the ball is Weitengning capsules.Through preliminary analysis in the plasma and urine of metabolic pathways and metabolites produced diversification and found 10 The metabolic pathways include isomerization,methylation,and hydroxyl groups.Further analysis revealed that the metabolites in the rat body could be further induced by the reaction of hydroxyl,methylation,methylation,and glucose. |
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