| Objective: To study the gastrointestinal absorption characteristics of the Xinjiang Pomegranate Peel Polyphenols’ Purification main components: punicalagins and ellagic acid, gastrointestinal absorption mechanisman punicalagins and ellagic acid in Pomegranate Peel Polyphenols’ were preliminary explored, provde the basis of bio-logical pharmacy of punicalagin and ellagic acid to clinical application and development of preparations. Methods:(1) Shaking flask-UV Pectro Photometry was establi-shed and used to detect the equilibrium solubility and the oil-water partition coeffi-cient of punicalagins and ellagic acid in different phosphate buffers with temperatur-e of 25 and 37℃.(2) Setting up content determination method for determination of two main components in the artificial gastric juice and artificial intestinal juice.(3)The isolated everted intestine model was used to study the absorption of punical-agins and ellagic acid in different regions of rat intestine、different drug concentrat-ionand and different time.(4) The rat gastric perfusion in situ model was used to s-tudy the stomach absorption situation of punicalagins and ellagic acid of pomegran-ate peel polyphenols’ purification, the determination of content by HPLC and calcul-ate the percentage of drug absorption in the stomach;(5) The rat in situ single-pass intestinal perfusion model was used to study the intestinal absorption situation of punicalagins and ellagic acid of pomegranate peel polyphenols’ purification, the determination of content by HPLC, to explore the influence of different mass concentra-tionon the absorption of punicalagins and ellagic acid in pomegranate peel polyphe-nols’ purification, at the same time to study the best absorption parts through the intestine test on two kinds of main ingredients in the pomegranate peel polyphenol s’ purification. The intestinal absorption mechanism of punicalagins and ellagic acid-in pomegranate peel polyphenols’ purification was preliminary analyzed. Results:(1) At 25℃, the equilibrium solubility of punicalagins were 7775.00±0.02~2789.00±0.01g·m L-1; in buffer solutions with p H values of 1.2-8.0, respectively, the equilib-rium solubility of ellagic acid were 1.01±0.01~8.14±0.02g·m L-1in buffer solutions with p H values of 1.2-8.0,respectively; the oil-water partition coefficient of punical-agins were-3.07~-3.85 in buffer solutions with different p H values; the oil-water partition coefficient of ellagic acid were-2.22~-3.20 in buffer solutions with different p H values; At 37 ℃, the equilibrium solubility of punicalagins were 1006.00±0.00~2684.00±0.00g·m L-1 in buffer solutions with p H values of 1.2-8.0, respective-ly, the equilibrium solubility of ellagic acid were 1.02±0.01~8.04±0.00g·m L-1 in b-uffer solutions with p H values of 1.2-8.0,respectivel; the oil-water partition coeffici-ent of punicalagins were-1.32~-3.81 in buffer solutions with different p H values,the oil-water partition coefficient of ellagic acid were-2.18~-2.44 in buffer soluti-ons with different p H values.(2)The method of specificity, linearity, precision, rec-overy, stability and adsorption were investigated, the results are in accord with the e-xperimental requirements.(3) The study results using isolated everted intestine model in situ of the absorption of punicalagins showed that: the intestine absorption r-ate constantly increased along with the increasing in concentration of punicalagins.Absorption of index components for punicalagins in different intestinal segments h-ad no significant difference, at low concentration, the absorption rate constant is il-eum > colon > jejunum > duodenum, at high concentration, jejunum > colon > il-eum > duodenum; every intestine segments cunmlative absorption increased along with concentration of punicalagins, at high concentration, every intestine segments c-unmlative absorption of punicalagins is 0.602±0.102, 0.643±0.587, 0.713±0.130, 0.730±0.114μg·cm-2.(4) The study results takingr rats gastric perfusion in situ model of the absorb of punicalagins and ellagic of pomegranate peel polyphenols’ purifica tion showed that: the mean absorption percentage each hour(%) in stomach of pomeg-ranate peel polyphenol extraction compounds’ punicalagins and punicalagin monomers were: low concentration, 11.68 ± 5.15, 11.80 ± 1.24; when the concentration is hig-h, 11.82 ±2.41, 13.02 ±4.22; the mean absorption percentage each hour(%) in stomac-h of po-megranate peel polyphenol extraction compounds’ ellagic acid and ellagic acid monomers were: low concentration, 11.96±2.18, 8.23±1.20; when the concentratio-n is high, 17.51±1.71, 5.74±1.43;(5) The study results carrying out rat single pass intestine perfusion in situ model of the absorb punicalagins and ellagic of pomegr-anate peel polyphenols’ purification showed that :the pomegranate peel polyphenol extraction compounds’ punicalagins and punicalagin monomers in different intestinal se-gments have absorption, the Ka(10-2min-1) of jejunum, duodenum, ileum and colon were: low concentration, 3.82±0.01, 2.47±0.01, 2.58±0.00, 1.08±0.00; 8.58±0.01, 6.13±0.02, 8.07±0.01, 5.19±0.02, when the concentration is high, 3.14±0.00, 3.57±0.02,1.77±0.00, 2.30±0.00; 7.69±0.01, 6.62±0.00, 6.30±0.001, 6.05±0.01; the Papp(10-3c m·min-1) of jejunum, duodenum, ileum and colon were: low concentration, 1.33±0.00, 1.23±0.00, 1.12±0.00, 0.89±0.00; 3.82±0.01, 2.47±0.01, 2.58±0.00, 1.08±0.00, wh-en the concentration is high, 0.80±0.00, 0.87±0.00, 0.74±0.00, 0.69±0.00; 3.14±0.00, 3.57±0.00, 1.77±0.00, 2.30±0.00; the pomegranate peel polyphenol extraction compounds’ ellagic acid and ellagic acid monomers in different intestinal segments have absorption, the Ka(10-2min-1) of jejunum, duodenum, ileum and colon were: low co-ncentration, 7.81±0.02, 6.32±0.01, 4.97±0.00, 4.68±0.02; 4.44±0.01, 8.60±0.05, 5.61±0.00, 3.92±0.01, when the concentration is high, 7.00±0.01, 7.96±0.00, 5.58±0.01,3.50±0.01; 7.11±0.00, 6.58±0.01, 7.02±0.06, 5.95±0.01;the Papp(10-3cm·min-1) of jeju-num, duodenum, ileum and colon were: low concentration, 1.09±0.00, 0.99±0.00, 1.05±0.00, 0.70±0.00; 0.88±0.00, 1.46±0.01, 1.21±0.00, 0.90±0.00, when the concentra-tion is high, 1.14±0.00, 1.17±0.00, 1.04±0.00, 1.38±0.01; 1.72±0.00, 1.39±0.00, 3.22±0.01, 1.90±0.001. Conclusion:(1) Punicalagin’s equilibrium solubility under acidic conditions, the solubility is basically constant increased along with the increasing w-ith of the p H values of the solutiont, this may be related to the presence of punica-lagins in the structure of the carboxyl group; at p H=2.5-5.0, its solubility increased, decreased between p H=5.0-5.8, and increases in p H=-5.8-7.8, this may be related to punicalagins on value of p Ka; in p H=1.2, the solubility of punicalagins was signific-antly lower than the solubility of other p H, saying that punicalagins dissolved in the stomach is not good, may affect the gastric absorption.ellagic acid solubility increased with the p H value increasing, the solubility of p H=6.8-8.0, dips, which may be relat-ed to the structure in the relevant ortho two hydroxyl; the p H value of 1.2-8.0 p H,the P of punicalagins and ellagic acid were less than-2, so the two are not easily through biological membranes, speculated that their absorption in the gastrointestinal tract is not ideal; temperature has little effect on t-heir equilibrium solubility and oilwater Partition coefficient.(2) The detection method is accurate, rapid and simple, to lay a methodological foundation for the study of gastrointestinal absorption in rats.(3) Punicalagin monomes, ellagic acid monomers are poorly absorbed in the stomach, and other components of pomegranate peel polyphenols’ purification basically has no influence on the absorption of punicalagin, ellagic acid in the stomach; absorption of punicalagins and ellagic acid didn’t be a special “absorption window”; the Ka and Papp of pomegranate peel polyphenols’ purification were higher than the monome-rs’, the Ka and Papp of ellagic acid monomesr and the ellagic acid in polyphenol e-xtraction have significant difference(P<0.05), composition in polyphenol extractions may be has played a catalytic role in ellagic acid’s absorption, but the punicalagin monomers and pomegranate peel polyphenol punicalagin refined there was no signi-ficant difference(P>0.05) in Ka and Papp of punicalagin monomesr and the punicalagins in polyphenol extraction. |
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