Two Wonderful Capsule Of The Preparation Process, Quality Standards And Pharmacokinetic Study

Purpose: 1. ErMiao pellet is changed from traditional system into a modern capsules, To optimize the best extraction process of Cortex Phellodendri in ErMiao capsules. 2. Extract matter of Rhizoma Atractylodis is isolated monomer compounds and applicated for the indicators for Atractylodes lancea. 3.To establish the qualitative and quantitative identification methods of the effective component, berberine in the Er Miao capsules. 4. There is a comparative study of the pharmacokinetics about ErMiao capsules and ErMiao pellet ,and main index of study is berberine. From the perspective of pharmacokinetics we can see the changes in plasma concentration about different formulations in animals.Material and method: 1. Materials: Cortex Phellodendri, purchased in Sichuan, identified as tree bark of Phellodendron chinense Schneid and Phellodendron amurense Rupr of Rutaceae. Atractylodes lancea, purchased in Hubei, identified as dry root of Atractylodes lancea and Atractylodes chinensis. 2. Methods:①Orthogonal design L₉(3⁴) was used to study the best extraction condition with the content of the synthesized evaluation of total extraction and berberine,to determine the best extraction process for Cortex Phellodendri. Extract the volatile oil by steam distillation, water , distillation time for the volatile oil extraction rate of the impact were investigated by using single factor. The study was carried out with orthogonal design. The optimum extraction craft of Rhizoma At ractylodis oil was choosed and the oil extraction rate were used as a index ; The optimum including technics was choosed by determining the oil-bearing rate and extract ratio of inclusion compound. The inclusion compound were identified with thin chromatogram.②Through silica gel column chromatography, gel column chromatography,and recrystallization, To isolate metamar compounds from the cyclohexane extract of Atractylodes lancea.③The use of high-performance liquid chromatography Ermiao content of berberine hydrochloride in capsules Column: kromasil5u C18 100A (250mm×4,6mm); column temperature:30℃; mobile phase:acetonitrile -0.025ml/Lphosphoric acid (55:45), flow rate: 1 .0ml/min;detected at 265nm.④After the rabbits are administered by ErMiao capsules and ErMiao pellet through ig.HPLC was used to determine berberine in blood plasma at different times, DAS2.0procedure is used to process concentration-time data. Results: 1. This experiment the best extraction process for Cortex Phellodendri was as follow: coarse powder,70 percent ethanol,refusing and extracting for 3 times, total 1.5 hours, 10folds of 70% ethanol. Dried into a paste filtrate swing, back-up. Herb medicine will be three hours of immersion, with ten times the volume of extraction of the hot water back to six hours, the collection of volatile oil, volatile oil will be used to prepareβ-cyclodextrinβ-Cyclodextrin Inclusion Complexes. The extraction technology was Rhizoma At ractylodis was smash to thick granula and extracted 6h with ten volume of water. The optimum preparation conditions for clathrate were established asβ-CD: oil was 6∶1, used 60ml of water, ultrasound for 45 minutes. Be crushed into a fine powder inclusion complex, back-up. After extraction of the herb dregs, the volume of water increases with the times and then extracted twice, each time 2 hours, filtration, the filtrate dried into a paste swing, back-up. Were obtained for uniform mixing, grinding, granulation with ethanol, drying, Whole, which was loaded capsules. 2. From extracts of Atractylodes lancea isolated two compounds. 3. To establish the HPLC determination berberine in the Er Miao capsules, its stability RSD value less than 1.37%, stability is good, 0.77μg-2.05μg in the framework is a good linear relationship. 4. In the rabbit plasma samples, the linear range of berberine is 0.00427-0.427μg·mL^-1, it has extract a high recovery rate, and days-day precision RSD is less than 10%. Er Miao pills Berberine largest in rabbits plasma concentration is 0.082μg·mL^-1, peak time is 8 hours, the drug molecules in the body 0-24 hours for the average residence time is 9.596 hours, the average absorption time is 23.972 hours, 0-24-hour AUC is 0.686mg / L * h; ErMiao capsules berberine in rabbits plasma concentration for the largest is 0.303μg·mL^-1, peak time is 5 hours, the drug molecules in the body an average of 0-24 hours duration is 7.282 hours for the average absorption time is 14.408 hours, 0-24-hour AUC is 1.00mg / L * h. The whole blood concentration—time course of berberine in ErMiao capsules is fitted to be a two-compartment model, and berberine in ErMiao pellet is fitted to be a one-compartment model.Conclusion: 1. The optimum technology condition of ErMiao capsules is reasonable and practicable for extraction. Its high efficiency is suitable for industrial production. 2. The first is old compound,the other is new compound. 3. The establishment of quality standards about ErMiao capsules supply a reliable control method for the preparation of the quality of analysis, the method is simple, rapid and accurate. Method is a good reproducible and exclusive. 4. This essay establishes a method for determine berberine in Cortex Phellodendri in rats plasma, provided the pharma—cokinetic parameters for rational administration of ErMiao capsules, and also provided the pharmacokinetic study method of compounds.