ABSTRACT
Huperzine A (Hup-A) is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) was used to enhance the oral bioavailability and lymphatic uptake and transport of Hup-A. A single-pass intestinal perfusion (SPIP) technique and a chylomicron flow-blocking approach were used to study its intestinal absorption, mesenteric lymph node distribution and intestinal lymphatic uptake. The value of the area under the plasma concentration-time curve (AUC) of Hup-A SMEDDS was significantly higher than that of a Hup-A suspension (<0.01). The absorption rate constant () and the apparent permeability coefficient () for Hup-A in different parts of the intestine suggested a passive transport mechanism, and the values ofandof Hup-A SMEDDS in the ileum were much higher than those in other intestinal segments. The determination of Hup-A concentration in mesenteric lymph nodes can be used to explain the intestinal lymphatic absorption of Hup-A SMEDDS. For Hup-A SMEDDS, the values of AUC and maximum plasma concentration () of the blocking model were significantly lower than those of the control model (<0.05). The proportion of lymphatic transport of Hup-A SMEDDS and Hup-A suspension were about 40% and 5%, respectively, suggesting that SMEDDS can significantly improve the intestinal lymphatic uptake and transport of Hup-A.
ABSTRACT
Objective To explore the optimal storage standard of fresh human milk, and to observe the influence of different cold storage condition (time-temperature) on macronutrients (fat, protein, carbohydrates, TS and energy), immune sub-stances (sIgA, lactoferrin, IL-6, 8, 10 and TNF-α) and bacteria indicators of fresh human milk.Methods Fresh milk samples (n=30) were divided and stored at three temperature and nine time points, which are 4℃ (24 h, 48 h, 72 h), -18℃(72 h, 7 d, 14 d, 4 w, 8 w, 12 w), and -80℃ (12 w, 24 w). At each time point, the macronutrients , immune substance, and bacteria colony counts of each milk sample were measured and compared with fresh milk. Results Compared with fresh milk, all indicators with the exception of lactoferrin in stored human milk showed signiifcant difference (P<0.05). Under 4℃ refrigeration condition, fat, IL-6, and TNF-α decreased, bacteria colony counts and Gram-positive colony counts increased over 72 h storage (P<0.05). Under-18℃ freezing condition, fat, protein, TS, energy and IL-6 decreased from 72 h to 12 w storage (P<0.05); carbohydrates and sIgA also decreased from 4 w and 8 w storage, respectively (P<0.05). Under -80℃ freezing condition, fat, protein, TS, energy and IL-6 decreased over 24 W storage (P<0.05).Conclusions The macronutrients, immune substance, and bacteria indicators of human milk were affected obviously by cold storage. Refrigerated at 4℃ should not be longer than 72 h, -80℃ freezing condition should be chosen for more than two months storage.
ABSTRACT
Aim To develop a sensitive,specific and accurate method for quantifying a novel derivate of all-trans-retinoic acid, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR)in rat tissues to investigate the tissue distribution of ATPR in rats.Methods Sprague-Daw-ley (SD)rats were killed by exsanguination at 2,4,7 h after a single intragastric administration with one dose of ATPR (20 mg·kg-1 )or at 5 min,1 h,5 h after a single intravenous administration with one dose of AT-PR (7 mg·kg-1 ).The concentration of ATPR in the tissues was determined by high performance liquid chromatography (HPLC)method.Results After the rats were administrated intragastrically, the highest concentration of ATPR was observed in intestine,fol-lowed by liver,spleen and lung,while the distribution in heart,kidney,fat and brain was very little.Howev-er,the highest concentration of ATPR was in liver after given intravenously,followed by spleen and lung,and very low in heart,kidney,intestines,fat and brain. Conclusion The distribution of ATPR is higher in liv-er after administrated both intragastrically and intrave-nously,suggesting the potential anti-proliferation and differentiation inducing effects of ATPR targeting at liv-er cancer.