RESUMO
The principle aim of this study was to design a controlled release (CR), bioadhesive formulation of miglitol (in form of pellets) which would regulate the post-prandial glucose levels via reversible inhibition of α-glucosidase enzyme as well as by modulating the glucagon-like peptide-1 (GLP-1) pathway in non-diabetic canines. A multilayered pellet formulation which was both bioadhesive (because of hydroxy propyl methyl cellulose polymer) and CR (because of the ethyl cellulose layer) was formulated. We report a novel finding that the CR formulation of miglitol (S3) induced a 2.2-fold elevation in the C(max) as well as the overall AUC(0-24) of GLP-1 values in comparison to the non-CR (immediate release (IR) formulation). The S3 formulation also resulted in better, steady, and prolonged control of glucose levels over a time period of 7 h in comparison to the IR formulation possibly due to combination of both, prolonged inhibition of the α-glucosidase enzyme and enhanced plasma GLP-1 levels. The S3 formulation was stable with no changes in the dissolution profiles at both of the stability conditions tested, 25°C/60% RH and 40°C/75% RH. Aqueous polymeric coating of the pellets (in contrast to coating using organic solvents) resulted morphologically in a uniform polymeric film and also releases profiles with lower burst effect. Curing played a significant role in determining release profile of the pellets, prepared by aqueous polymeric coating method.
Assuntos
1-Desoxinojirimicina/análogos & derivados , Carboidratos da Dieta/farmacologia , Células Enteroendócrinas/metabolismo , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Intestino Delgado/metabolismo , 1-Desoxinojirimicina/administração & dosagem , 1-Desoxinojirimicina/química , 1-Desoxinojirimicina/farmacocinética , Animais , Disponibilidade Biológica , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Celulose/análogos & derivados , Celulose/química , Preparações de Ação Retardada , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cães , Implantes de Medicamento , Células Enteroendócrinas/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases , Intestino Delgado/efeitos dos fármacos , Masculino , Metilcelulose/química , Polímeros/química , Período Pós-Prandial , Ratos , Ratos Sprague-Dawley , alfa-Glucosidases/metabolismoRESUMO
OBJECTIVE: To extract and isolate chemical constituents from the total alkaloids of silkworm dropping (Can Sha) of Bombyx mori L. METHODS: Chemical constituents were isolated by column chromatography with macroporous adsorbent resin, ion-exchange resin and sephadex LH 20. The structures of the isolated compounds were determined by spectral means. RESULTS: Three compounds were isolated and identified as 1-deoxynojirimycin (1) , fagomine (2) , and 3-epifagomine (3) on the basis of their 1H-NMR, 13C-NMR spectra and ESIMS data. CONCLUSION: Compounds 1-3 are isolated and identified from Can Sha for the first time.