ABSTRACT
Objective: Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Salvia miltiorrhiza for cirrhosis. Methods: TCMSP database was utilized to obtain the active components of S. miltiorrhiza. Through GeneCards, OMIM and DRAR-CPI, the potential targets of S. miltiorrhiza for the treatment of cirrhosis were screened. Cytoscape 3.6.0 software was established to construct the active components-targets network of S. miltiorrhiza. STRING database and Generate style from statistics of Cytoscape 3.6.0 software were conducted to draw a graph of protein interaction network. Molecular docking was carried out through Systems Dock Web Site with the active components of S. miltiorrhiza. The GO classified enrichment analysis and the KEGG pathway enrichment analysis were performed by using DAVID database. Results: Selecting the OB ≥ 30% and DL ≥ 0.18 as filter condition, 65 active components and 75 targets of S. miltiorrhiza were involved. S. miltiorrhiza exerted its effects on treating cirrhosis mainly by regulating signaling pathways including MAPK, Toll-like receptor, Gap junction, PI3K/AKT, Natural killer cell mediated cytotoxicity signaling pathway and so on. Conclusion: This study preliminarily predicted the major targets and pathways of S. miltiorrhiza acting on cirrhosis, which provided new ideas and clues for its further research.
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OBJECTIVE: Compared with the compound captopril tablets (compound Cap), to study the pharmacokinetics characteristics and bioavailability in twelve wista rats after oral administration of Cap pulsed pellets and compound CAP tablets by HPLC. METHODS: To prepare captopril pulsed pellets (Cap pulsed pellets). The pharmacokinetic parameters were computed by software program DAS2.1. RESULTS: In vivo the lag time for 4.75 h, compared with ordinary tablet, it has an obviously lag time, tmax was 9.67 h and the relative bioavailability was(117.29 ± 46.87)%. CONCLUSION: The release of CAP from CAP pulsed sustained-release pellets was shown to be sustained-release after an conspicuous lag time in vitro and in vivo. So the drug can be taken by the patient before sleeping and can achieve the purpose in the morning. Copyright 2012 by the Chinese Pharmaceutical Association.
ABSTRACT
The aim of this study was to develop a sustained release converse thermosensitive hydrogel for intra-articular injection using chitosan-glycerol-borax as matrix, its physical properties and biocompatibility were investigated. Taking gelation time and gelation condition as index, the influence of concentration of chitosan, ratio of chitosan to glycerol, pH on physical properties of hydrogel were investigated. And then the in vitro drug release, rheological properties and biocompatibility were studied. The thermosensitive hydrogel flows easily at room temperature and turns to gelation at body temperature, which can certainly prolong the release of drug and has good biocompatibility.
Subject(s)
Animals , Male , Rats , Analgesics , Chemistry , Chitosan , Chemistry , Delayed-Action Preparations , Drug Compounding , Hydrogels , Chemistry , Hydrogen-Ion Concentration , Inflammation , Injections, Intra-Articular , Knee Joint , Materials Testing , Plants, Medicinal , Chemistry , Rats, Sprague-Dawley , Rheology , Seeds , Chemistry , Strychnine , Chemistry , Strychnos nux-vomica , Chemistry , Surface Properties , Synaptic Membranes , TemperatureABSTRACT
To explore the mechanism of the absorption enhancement of borneol, the effect of borneol on the intestinal absorption and the pharmacokinetics of tetramethylpyrazine phosphate after oral administration were investigated. In situ intestinal recirculation was performed to study the effect of various concentrations of borneol on the absorption of tetramethylpyrazine phosphate at duodenum, jejunum, ileum and colon. After oral administration of tetramethylpyrazine phosphate, the mixture of tetramethylpyrazine phosphate and borneol and the mixture of tetramethylpyrazine phosphate and verapamil in rats, the concentrations of tetramethylpyrazine phosphate in plasma were determined by RP-HPLC at predesigned time. The pharmacokinetic parameters were compared based on the results of the three animal experiments, and analyzed with software program 3p97. The result showed that tetramethylpyrazine phosphate could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows: colon > duodenum > jejunum > ileum, but without saturation, which demonstrated that tetramethylpyrazine phosphate was absorbed via simple diffusion. Borneol could enhance the intestinal absorption of tetramethylpyrazine phosphate, however, not in proportion. There was no obvious difference between the test group and the control group when 10 microg x mL(-1) borneol was added (P > 0.05), while when the concentration comes to 25 microg x mL(-1) and 50 microg x mL(-1), significant differences were observed (P < 0.05). Borneol and verapamil did enhance the bioavailability of tetramethylpyrazine phosphate after oral administration in rats. The enhancing effect of borneol showed only when the concentration came to a certain level but with no specific sites existed in the intestine. One of the mechanisms of borneol on the enhancing effect on absorption of tetramethylpyrazine phosphate might be the inhibition of the metabolism of CYP 3A and exocytosis of P-gp.
Subject(s)
Animals , Male , Rats , Biological Availability , Camphanes , Pharmacokinetics , Herb-Drug Interactions , Intestinal Absorption , Pyrazines , Pharmacokinetics , Rats, Sprague-DawleyABSTRACT
<p><b>AIM</b>To prepare verapamil hydrochloride controlled-onset extended-release pellets (VH-COERP) and study its release behavior in vitro. To compare the pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of VH-COERP and verapamil hydrochloride delayed-release pellets (VH-DRP) as reference.</p><p><b>METHODS</b>The core of VH-COERP were prepared in the fluidized bed (mini-glatt) by spraying water solution containing drugs onto sucrose-starch pellets with hydroroxy propyl methyl cellulose (HPMC) as the inner coating swelling layer and ethylcellulouse aqueous dispersion as the outer coating controlled layer. Through modifying the coating level of inner and outer layer, the VH-COERP with the optimized cumulative release profile was obtained. The concentration of VH in plasma of six dogs and its pharmacokinetic behaviors after oral administration of VH-COERP and VH-DRP at different times were studied by RP-HPLC. The pharmacokinetic parameters were computed by software program 3P97.</p><p><b>RESULTS</b>The lag time, the release behavior and the amount of VH from VH-COERP within 24 hours were not influenced by the pH of dissolution medium and post-process, but obviously influenced by the different kinds of added material in swelling layer and the coating level of the inner swelling layer and the outer controlled layer. In vitro the lag time of release profile of VH from VH-COERP was 5 h and then VH was extended release from VH-COERP in the following time. Compared with the VH-DRP, VH-COERP in vivo has an obviously lag time (4 h) , Tmax was also delayed (8 h) and the relative bioavailability was (94.56 +/- 7.64)%.</p><p><b>CONCLUSION</b>The release profile of VH from VH-COERP was shown to be extended-release after an conspicuous lag time in vitro and in vivo. So the drug can be taken by the patient before bed time and begin to work at the morning.</p>