RESUMO
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.
Assuntos
Animais , Camundongos , Ratos , Química Farmacêutica , Ácido Desoxicólico , Química , Portadores de Fármacos , Química , Estabilidade de Medicamentos , Micelas , Tamanho da Partícula , Peptídeos , Química , Farmacocinética , Fosfolipídeos , Química , Ratos Wistar , Timo , QuímicaRESUMO
<p><b>OBJECTIVE</b>To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate (ANIT)-induced experimental hepatic injury after oral administration of Yinchenhao Decoction (, YCHD) using an ultra pressure liquid chromatography (UPLC) method.</p><p><b>METHODS</b>Rats were divided into a normal group and a model group, after modeled by 4% ANIT (75 mg/kg) for 48 h, they were orally administrated with YCHD extract at the dose of 0.324 g/kg, and then blood was collected from their orbital sinus after different intervals. Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] and bilirubins [total bilirubin (TBIL), direct bilirubin (DBIL)], the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC, and the pharmaceutical parameters were calculated with DAS2.1.1 software.</p><p><b>RESULTS</b>The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained. Their time to maximum plasma concentration (t(max)) were both 0.25 h, the maximum concentration (C(max)) were 4.533 μg/mL and 6.885 μg/mL, and their area under concentration-time curve (AUC)(0→24h) were 16.272 and 32.981, respectively. There was a 51.88% and 100.46% increase in C(max) and AUC(0-t) (P<0.05), but there showed a 45.52% and 92.93% reduction in clearance of drug and volum of distribution (P<0.05), respectively.</p><p><b>CONCLUSIONS</b>Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD, the absorption and distribution process was accelerated in liver injured rats, but the metabolism and elimination process was slowed. And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.</p>
Assuntos
Animais , Ratos , 1-Naftilisotiocianato , Administração Oral , Doença Hepática Induzida por Substâncias e Drogas , Sangue , Tratamento Farmacológico , Metabolismo , Cumarínicos , Sangue , Farmacocinética , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas , Farmacocinética , Usos Terapêuticos , Fígado , Modelos Biológicos , Ratos Sprague-Dawley , Estudos de Validação como AssuntoRESUMO
To compare the microcalorimetric fingerprint profiles of Lonicerae japonicae Flos (Lj.F) and Lonicerae Flos (L.F), microcalormietry was applied to find the heat change regularity of Bacillus shigae (B. shigae) metabolism affected by Lj.F and L.F (we choose Lonicera macranthoides Hand.-Mazz in this paper) with different concentrations. The thermogenic curves and thermodynamics parameters were investigated as evaluation index, and then the date of experiment was studied by similarity analysis. All the results indicated that the Lj.F and Lonicera macranthoides Hand.-Mazz (L.m.H-M) significantly impacted the microbial growth and had good similarity in its inhibitory activities. The combination approach of chemical analysis with bioassay was developed and employed to ensure the safety and efficacy of Chinese herbal medicines.