| Objective:The characteristics of traditional Chinese medicines (TCMs) which contain multiple components and targets have been widely recognized. In recent years, the relevance of quality and efficiency and the concept of quality by design (QBD) have been used on the quality control of TCMs much more than before. As a consequence, it is a research focus that considering the characteristics of TCM and its clinical curative effect for quality control and evaluation. However, the drug effect is closely related not only to the content of the components, but also with the absorption process. Biopharmaceutics classification system (BCS) is a scientific framework focused on the water solubility and intestinal permeability of drugs and these two important parameters are related to drug absorption characteristics in biopharmaceutical research. It can be used for screening candidate compounds, designing formulation and the bioequivalence immunity for the generic drugs, etc. Most components that BCS studied were absorbed by intestine. They produced the healing efficacy when reached the targets. But the research about the components which exert direct effects on the targets before absorbed by intestine is less. It is uncommon that combine the BCS with efficacy to research on oral absorption of TCM under the background of the study on its multiple components and multiple targets. Therefore, this paper chose Coptis chinensis Franch. as the research object to study its properties of biopharmaceutics classification.The study was carried out in the premise of ensuring its effective components and guaranteeing the stability and uniformity of components’content. This paper studied the solubility of Coptis extract and the hypoglycemic activity of Coptis extract was taken into account in the study of its permeability. In the test, the ratio of content and half maximal inhibitory concentration IC50 was the weight factor to calibrate and calculate the permeability of each ingredient in TCM. The properties of Coptis can be quantitative evaluation eventually. This paper analyzed the effect factors of oral absorption and targets before absorbed by intestine of Coptis through the BCS. It will accumulate data and research experiences for the study of biopharmaceutics classification system of Chinese materia medica (CMMBCS) and provide a new research idea in order to improve the quality standards of TCM.Methods:An analysis method for the content of alkaloids in Coptis was estabilished; methods of everted gut sac (EGS) and intestinal perfusion with venous sampling (IPVS) were used to preliminary identified the components in the aqueous extract which can be absorbed through the intestinal wall and absorbed into blood; the extraction and purification process were optimized by heating reflux extraction method and macroporous resin adsorption method in order to prepare the coptis extract; solubility of Coptis extract in different pH mediums were detected by shake flask method in Chinese Pharmacopoeia; the permeability of Coptis extract was determined by single-pass intestinal perfusion (SPIP) while the a-glucosidase inhibition test in vitro was used to obtain weight coefficients.Results:1. Determination of multiple components in Huanglian decotion absorbed by intestine. Seven alkaloids (magnoflorine, columbamine, epiberberine, jatrorrhizine, coptisine, palmatine and berberine) of the aqueous extract can be absorbed through the intestinal wall and absorbed into blood. These components absorbed into intestine and blood were less and their intestinal permeability were poor. EGS experiments showed that the absorption of alkaloids in the duodenum were good, the second were the ileum and colon and the last was jejunum.2. Preparation of Coptis Root extract for subsequent research. ①The effect of ethanol concentration on the extraction of Coptis was the most significant through single factor experiment combined with orthogonal experiment design. The reflux extraction was extracting with 80% ethanol for two times and each time for one hour with fluid volume for 10 times. The content of total alkaloids in crude extracts of Coptis was 38.77%. ② AB-8 macroporous resin was used to explore the optimal purification condition of crude extracts. The best combination of process parameters were obtained. Diameter-height ratio was 1:7, the concentration of the sample solution was 0.05 g·mL-1, the sample volume was 4.5 times of resin volume, adsorption velocity was 1.0 mL·min-1, the volume of water used to wash resin was 1 times of resin volume and the volume of 50% ethanol used to desorb alkaloids was 4 times of resin volume.3. The research on BCS properties of the Coptis extract. ①The solubility of the alkaloids in the extract showed the basically trend of increase with the increase of pH value through pH-solubility diagrams of alkaloids and their change trends of the solubility were similar. The solubility of the alkaloids in the extract and the solubility of every single component in pH 7.4 buffer were a significant change. That is to say, the solubility of alkaloids in the extract can be effected by multicomponent environment obviously. The solubility of the extract in pH1.0 buffer solution was 15.693 mg·mL-1, and the dose number, Do, was 0.201. Synthesize the above results, the Coptis extract belonged to high solubility according to BCS. ②The results of a-glucosidase inhibition test displayed that only the Coptis extract, jatrorrhizine and palmatine had weak inhibitory activity with the inhibition rates less than 20%. Therefore, IC50 were all defined as 1 and content of alkaloids became the main factor to calculate weight coefficients for permeability. The effective permeability coefficient Peff of alkaloids were less than 0.5x10-4cm·s-1, no matter the single component or the alkaloids in the extracts. They were all classified as low permeability. The statistical analysis results showed that multicomponent environment had no significant effect on the permeability of alkaloids in Coptis. The Peff of Coptis extract in jejunum was 0.146×10-4 cm·s-1, and it was also a drug with low permeability according to the BCS.Conclusion:The Coptis extract belonged to BCS class III and its maximum absorbable dose MAD was 88.55 g; the inhibition on a-glucosidase was not the only mechanism for the hypoglycemic effect of Coptis, and the solubility of alkaloids in it under multicomponent environment was beneficial to exert its inhibitory effect on a-glucosidase.Features and innovation points of this paper are as follows:l.The data of a-glucosidase inhibitory activity in vitro experimental,the water solubility and intestinal permeability of Coptis Root extract were analyzed;2.The BCS attribute of Chinese herbal extracts was studied, and the relevant mathematical formula for BCS was applied and verified based on Coptis Root extract. |
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