ABSTRACT
Ischemic brain injury is a major disease which threatens human health and safety. (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T), a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/polyvinylpyrrolidone (PVP) solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry (DSC), infrared spectroscopy (IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM). The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1:5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.
Subject(s)
Benzoates/chemistry , Drug Delivery Systems , Povidone/chemistry , Benzoates/administration & dosage , Brain Ischemia/drug therapy , Chemistry, Pharmaceutical/methods , SolubilityABSTRACT
A series of 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (7a-7q) have been designed, synthesized and evaluated for their antitumor activity. Most of the synthesized compounds were proved to have potent antitumor activity and low toxicity. Among them, compound 7a showed the most potent biological activity against Human Umbilical Vein Endothelial cells, which was comparable to the positive control. The results of apoptosis and flow cytometry (FCM) demonstrated that compound 7a induce cell apoptosis by the inhibition of MetAP2 pathway. Molecular docking was performed to position compound 7a into MetAP2 binding site in order to explore the potential target.
Subject(s)
Aminopeptidases/antagonists & inhibitors , Antineoplastic Agents/pharmacology , Dioxanes/chemistry , Enzyme Inhibitors/pharmacology , Glycoproteins/antagonists & inhibitors , Oxadiazoles/pharmacology , Protease Inhibitors/chemical synthesis , Protease Inhibitors/pharmacology , Aminopeptidases/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Glycoproteins/metabolism , Human Umbilical Vein Endothelial Cells/enzymology , Humans , Methionyl Aminopeptidases , Models, Molecular , Molecular Structure , Oxadiazoles/chemical synthesis , Oxadiazoles/chemistry , Protease Inhibitors/chemistry , Protease Inhibitors/classification , Structure-Activity RelationshipABSTRACT
To establish a fingerprint of Xiaochaihu granules sold in the market with HPLC method, and study fingerprints of Xiaochaihu granules produced by different manufacturers and in different batches of the same manufacturer. Seven major index components were identified for the first time. The established method provided an all-around analysis on the quality assessment of Xiaochaihu granules.
Subject(s)
Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/analysis , China , Quality ControlABSTRACT
To establish an appropriate experimental and data processing method on the basis of the general kinetic model for extraction of traditional Chinese medicines, in order to study the effect of total flavonoids in water extracts from Puerariae Radix on the adaptability of the model, with total flavonoids of Puerariae Radix as the determination indicator. The results showed that the natural logarithm of mass concentration of total flavonoids showed a good linearity with the changes in extraction time and solvent volume. Through calculating and fitting, we successfully established the kinetic model for water extraction of total flavonoids from Puerariae Radix, and verified its accuracy. Its good fitting degree and controllable deviation within the range of industrial production requirements indicated a good adaptability of the model. However, its equation correction factors require further studies.
