Studies On The Intestinal Absorption Kinetics And Regulatory Mechanism Of Feng Shi Soft Capsule

The purpose of this study is to investigate the absorption kinetics and regulatory mechanism of Feng Shi soft capsule, which will provide theoretical basis for selecting oral preparations, optimizing techniques, screening prescriptions, clinical application, and so on. In this paper, using curcumin as the marker compound, Caco-2 cells model, in situ perfusion model of rats and drug plasma concentration test were established to research the absorption characteristics and mechanism of Feng Shi soft capsule. There were four parts in our research:in situ perfusion model.of rats, Caco-2 cells model, drug plasma concentration test and evaluating the relation of three models.1. To determine the content of curcumin and phenolsulfonphthalein in the solution of in situ intestinal loop, an analytical method based on high performance liquid chromatography (HPLC) had been established with a Symmetry TM Shield R18 (5.0μm,4.6mm×250mm). The mobile phase was acetonitrile-4% glacial acetic acid solution (44:56) and the column temperature was set at 30℃. The flow rate was 1.0 ml/min with detective wavelength of 430 nm. This method is simple, rapid and accurate, which can provide testing techniques for the study of intestinal absorption kinetics of Feng Shi soft capsule.2. The absorption kinetics was investigated using the method of in situ perfusion in rats and the samples were determined by HPLC. The result showed that curcumin was absorbed quite well at all segments of intestine in rats and no specific absorption was found in different segments. When the concentration of perfusion solution was increased, contrarily the absorption rate constant (Ka) at the same level. Compared Ka of three different concentration of perfusion solution with variance analysis method, Ka of curcumin had no significant differences (p>0.05). In the range of 6.0～8.0, pH had no influence to the absorption of curcumin. The absorption of curcumin complied with the passive transport and first order kinetics.3. Using Caco-2 cell model, the transportations of curcumin in the Feng Shi soft capsule were studied from apcid side to basolateral side or from basolateral side to apical side. The result appeared that the apparent permeability (Papp) of curcumin in the high and low sample solutions from apical side to basolateral side respectively were (0.3959±0.23)×10-6cm.s-1, (0.3580±0.0693)×10-6cm.s-1, and had no significant differences (p>0.05) which had indicated that the transport of curcumine had not been affected by the concentration of Feng Shi soft capsule. The transport of curcumin was positively correlated to transport time and concentration. The curcumin in the Feng Shi soft capsule was mainly absorbed via passive transport, and belonged to medium absorbed compound. Meanwhile curcumin may have not been involved in efflux mechanism in Caco-2 cells monolayers model from the BL to AP side direction.4. By comparison of main absorption parameters and mechanism of curcumin, we found that Caco-2 cells model and in situ perfusion model of rats had well qualitative but bad quantitative relation. The result of absorption in vivo was profoundly different from another two models.In summary, curcumin in the Feng Shi soft capsule was absorbed and transported well, and the absorption mechanism may be passive transport. The concentration and pH had no influence to the absorption. Curcumin was absorbed quite well at all segments of intestine and no specific absorption was found in different segment. It may be suitable for sustained-release preparations to reduce the times of administration. However, pretending the detained time in the colon and posterior segment of small intestine must be considered to enhance the bioavailability. In addition, curcumin in the Feng Shi soft capsule may be not the substrate of p-gp, and the bioavailability of curcumin may be not affected by the excretion of P-gp. In order to elevate the bioavailability of curcumin in the Feng Shi soft capsule, conjugase inhibitors can be added to the preparation. The reason is that curcumin potentially is metabolized by the intestinal cells.It is rarely reported to research the absorption mechanism and influencing factors of TCM formulas by multi-angle and multi-biopharmaceutical modes. There is little literature about the preparation design of TCM under the guidance of biopharmaceutical principles. This study enriched the content of biopharmaceutics and pharmacokinetics and prepared for the development of Feng Shi soft shell capsule. Meanwhile, it provided new approaches and train of thought for the in vivo research of TCM formulas.