Comparison of anti-bacterial activity of three types of di-O-caffeoylquinic acids in Lonicera japonica flowers based on microcalorimetry

The anti-bacterial activities of three types of di-O-caffeoylquinic acids(diCQAs) in Lonicera japonica flowers, a traditional Chinese medicine(TCM), on Bacillus shigae growth were investigated and compared by microcalorimetry. The three types of diCQAs were 3, 4-di-O-caffeoylquinic acid(3, 4-diCQA), 3, 5-di-O-caffeoylquinic acid(3, 5-diCQA), and 4, 5-di-O-caffeoylquinic acid(4, 5-diCQA). Some qualitative and quantitative information of the effects of the three diCQAs on metabolic power–time curves, growth rate constant k, maximum heat-output power Pm, and the generation time tG, total heat output Qt, and growth inhibitory ratio I of B. shigae were calculated. In accordance with a thermo-kinetic model, the corresponding quantitative relationships of k, Pm, Qt, I and c were established. Also, the half-inhibitory concentrations of the drugs(IC50) were obtained by quantitative analysis. Based on the quantity–activity relationships and the IC50 values, the sequence of inhibitory activity was 3, 5-diCQA > 4, 5-diCQA > 3, 4-diCQA. The results illustrate the possibility that the caffeoyl ester group at C-5 is the principal group that has a higher affinity for the bacterial cell, and that the intramolecular distance of the two caffeoyl ester groups also has an important influence on the anti-bacterial activities of the diCQAs.

Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method

AIM： To improve the absorption and bioavailability of baicalin using a nanocrystal （or nanosuspension） drug delivery system. METHODS： A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo. RESULTS： The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of-34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 ug·mL-1, was much higher than the baicalin-microcrystals and the physical mixture （135 and 86.4 ug·mL- 1, respectively）. In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability （with the AUC（0-t） value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L-1·h-1, respectively）. CONCLUSION： The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure baicalin coarse powder and micronized baicalin.

Rational Daily Administration Times of Yinchenhao Decoctionin Rats with Jaundice Based on PD/PK

Objective To study the rational daily administration times of Yinchenhao Decoction(YCHD)when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model.Methods Rats were modeled by 4%1-naphthylisothiocyanate(75 mg/kg)for 48 h,then YCHD was drenched with doses of 0.324 g/kg (extract,calculated with the clinical dosage)once,0.162 g/kg twice,and 0.108 g/kg thrice a day,respectively.The total bile and the flow rate of bile were observed after the first administration;Blood samples collected from the orbital sinus at different intervals were used to investigate the levels of liver enzymes(ALT and AST)and bilirubins (TBIL and DBIL),and determine the concentration of 6,7-dimethoxycoumarin(DME)in the plasma using UPLC at the same time,then we obtained the time-effect and time-dose curves.The rational daily administration times of YCHD when treating experimental jaundice were determined based on the comprehensive analysis of time-effect and time-concentration relationships.Results Within 10 h the total bile of rats which were administered once daily(G1) was 1.65 and 1.33 times higher than that of twice and thrice(G2 and G3)a day,respectively,and the four biochemical indexes(TBIL,ALT,DBIL,and AST)of G1 decreased faster than those of G2 and G3(P<0.05).On the other hand, the blood drug level of DME when administrated once daily could maintain at a higher level for a longer time,and its Cmax and AUC0→t were higher than those of G2 and G3,which might be the main reason why its effect was the most significant.Conclusion It is more appropriate to administrate once daily when YCHD is used to treat jaundice.

Mixed nanomicelles loaded with thymopeptides-sodium deoxycholate/phospholipid improve drug absorption

AIM: To improve the absorption of thymopeptides(TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles(SDC/PL-MMs). METHODS: TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy(PCS), zeta potential measurement, as well as their physical stability after storage for several days. Furthermore, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties. RESULTS: A narrow size distribution of nanomicelles, with a mean particle size of(149 ± 8.32) nm and a zeta potential of(-31.05 ± 2.52) mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice. CONCLUSIONS: TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.