| Objective:The aqueous solubility and intestinal permeability of drugs are the important factors for drug absorption, also two key attributes of Biopharmaceutics Classification System Research (Biopharmaceutics Classification System, BCS), Biopharmaceutics Classification System is mainly aimed at simplification drugs research at present, is not applicable for many composition of traditional Chinese medicine. Most of traditional Chinese medicine is administered orally, in view of multi-component characteristics of traditional Chinese medicine, Biopharmaceutics Classification System of Chinese Materia Medica (Biopharmaceutics Classification System of Chinese Materia Medica, CMMBCS) theory was proposed by our group. because of the many types of traditional Chinese medicine, at the beginning of the study needs from simple to complex, from easy to difficult to study, in the early research requires the use of classical prescription and more in-depth study of basic, clinical still using, and the active ingredients of compound ingredients clearly and higher targets for the study, so this thesis under the guidance of Biopharmaceutics Classification System of Chinese Materia Medica and Gegenqinlian was taken as a carrier, the main object of study is berberine that is one component of high content of Gegenqinlian decoction, it is main efficacy component of coptis. Then take progressive research process from berberine single component and combination with the other high content components of Gegenqinlian decoction (puerarin, baicalin, glycyrrhizic acid) to single coptis herbs and then the Gegenqinlian decoction to carry out studies. In order to study Biopharmaceutics Classification System classification properties of berberine of Gegenqinlian decoction change under different environment and clarify its solubility and intestinal absorption characteristics, establish the general methodology of Biopharmaceutics Classification System of Chinese Materia Medica, to provide data to support the further development of Biopharmaceutics Classification System of Chinese Materia Medica.Methods:To establish effective analysis method of berberine single component, berberine in Coptis decoction and berberine in Gegenqinlian Decoction for the determination of berberine content in party, the shake flask method and high performance liquid chromatography (HPLC) method for determination of berberine solubility at different pH and berberine solubility changes by adding other ingredients of Gegenqinlian Decoction, the establishment of a multi-component model of berberine solubility to predict the solubility of berberine in compound; using the paddle method investigated the intrinsic dissolution rate of a single component berberine; using shake flask method and high performance liquid chromatography (HPLC) method for determination of oil-water partition coefficient of berberine single composition and related components compatibility; everted gut sac is adopted to to conduct qualitative research on the intestinal absorption; Single-pass intestinal perfusion method was used for quantitative studying of intestinal absorption; Intestinal perfusion with venous sampling for qualitative and quantitative studying of drug was absorbed into the bloodstream; the PAMPA method is adopted to determine the permeability in vitro.Results:(1) Berberine single ingredients with low solubility, berberine solubility increases with the increase of buffer pH, in pH7.4 the maximum is 3.57 mg/mL; berberine at different pH of the dissolution medium characteristic dissolution rate was less than 1 mg/min/cm2, and with the increase of pH increases. Berberine oil-water partition coefficient at different pH values are low, at pH1.0 partition coefficient 1gP maximum is -0.57, under the environment of baicalin and Gegenqinlian Tablets can make its coefficient has increased significantly in a pH of 4.0 to 7.4 phosphate buffer partition. Berberine is mainly better absorption in the upper small intestine, as berberine concentration increased, the absorption rate increases; permeability coefficient P eff of 80μg/mL berberine in jejunum was 0.104×10-4 cm/s, the rate of absorption constant Ka was 1.159×10/s; absorbed into the bloodstream of the permeability coefficient Pbiood was 0.111×10-7 cm/s, berberine may be passive diffusion transport mechanism in the small intestine.(2) Other index components (puerarin, baicalin, glycyrrhizic acid) of Gegenqinlian decoction to join in has a certain influence on solubility and permeability of berberine, puerarin and baicalin antagonism to its solubility at pH7.4, glycyrrhizic acid promoted, glycyrrhizic acid with baicalin and baicalin with puerarin have interacted influence on the solubility of berberine; Puerarin and baicalin can promote the absorption of berberine in the jejunum; by comparing the results of different permeability model showed that in addition to the passive diffusion of berberine may also exist other impact absorption mechanism. Through regression analysis of multi-component ratio solubility, permeability P eff and absorption fraction Fa showed that the impact of berberine multi-component Ratios Peff for Fa has significant.(3) The solubility and permeability of berberine has a certain promotion under coptis decoction and Gegenqinlian decoction, the absorption rate of berberine in Gegenqinlian decoction and coptis decoction was increased with drug concentrations increase. When a single component with a considerable concentration of berberine, permeability P eff of berberine in coptis decoction was 0.142×10-4cm/s, the absorption rate constant Ka was 1.583×10-4/s, bloodstream permeability Pblood was 0.411×10-7cm/s; the permeability Peff of berberine in Gegenqinlian decoction was 0.224×10-4cm/s, the absorption rate constant Ka was 2.493×10-4/s, bloodstream permeability coefficient Pblood was 1.170×10-7 cm/s, absorption of berberine in compound> single herbs> single component.Conclusion:berberine belongs to the low solubility and low permeability, berberine single component can be classified as BCS Ⅳ namely CMMBCS-Ⅳ; its solubility and dissolution increases as the buffer of pH increases, the oil and water distribution coefficient was low, showed its intestinal absorption was limited; the CMMBCS classification properties results of berberine through different environments showed that solubility and permeability changed but no significant improvement according to standard of BCS under the compatibility with the high content component of Gegenqinlian prescription, it can be classified as CMMBCS-IV in a multi-component compatibility environment. At coptis decoction environment, solubility and permeability changed not much, which in Coptis decoction classified as CMMBCS-IV, solubility and permeability has improved in Gegenqinlian decoction, but magnitude of change was small, it was classified as CMMBCS-IV in Gegenqinlian decoction.This study used several different permeability model for the study of absorption characteristics of berberine in different environments, and by comparing and analysis of the results showed that berberine has better absorption in the upper small intestine, mainly passive diffusion, may also be affected by other absorption factors. The root causes poor absorption of berberine poor permeability, solubility, although the absorption of impact, but not the core factors leading to poor absorption of berberine.Gegenqinlian prescription ingredients and other high content of berberine CMMBCS different environmental classification has certain properties of solubility and permeability the effects vary in different environments, but not across the CMMBCS-Ⅳ. There is no exact data about specific CMMBCS classification standard, and BCS classification standards, the classification of CMMBCS standards also need to constantly accumulate the more data and summed up the general standard.
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