Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1 A(R2), was accomplished. The drug showed signifi...Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1 A(R2), was accomplished. The drug showed significant degradation under hydrolysis(acidic, alkaline) and oxidation(peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products(DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by ~1H NMR,^(13)C NMR, 2 D NMR, Q-TOF-MSnand IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.展开更多
Phenylboronic acid (PBA) based glucose-responsive materials have attracted great interests in recent years for developing insulin delivery systems.It is desired to obtain PBA based materials that can response to gluco...Phenylboronic acid (PBA) based glucose-responsive materials have attracted great interests in recent years for developing insulin delivery systems.It is desired to obtain PBA based materials that can response to glucose under physiological pH and understand the mechanism.By using 11B triple-quantum magic-angle spinning nuclear magnetic resonance (11B 3Q MAS NMR) measurements,the glucose-responsive mechanism of micelles self-assembled from poly(ethylene glycol)-b-ploy(acrylic acid-co-acrylamidophenylboronic acid) PEG-b-P(AA-co-AAPBA) is deeply investigated.Different configurations of phenylboronic acid during various steps of glucose-responsive behaviors are clearly analyzed in the 11B 3Q MAS NMR spectra and coordination between carboxyl and PBA is confirmed.By increasing the AA units in PEG-b-P(AA-co-AAPBA),the carboxyl can coordinate with PBA moieties and cause the glucose-responsiveness of micelles even in the weak acid environment.展开更多
文摘Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1 A(R2), was accomplished. The drug showed significant degradation under hydrolysis(acidic, alkaline) and oxidation(peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products(DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by ~1H NMR,^(13)C NMR, 2 D NMR, Q-TOF-MSnand IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.
基金We are grateful to the National Natural Science Foundation of China (Nos.21274001 and 91127045),the National Basic Research Program of China (973Program,No.2011CB932503),and PCSIRT (IRT 1257)for financial support.
文摘Phenylboronic acid (PBA) based glucose-responsive materials have attracted great interests in recent years for developing insulin delivery systems.It is desired to obtain PBA based materials that can response to glucose under physiological pH and understand the mechanism.By using 11B triple-quantum magic-angle spinning nuclear magnetic resonance (11B 3Q MAS NMR) measurements,the glucose-responsive mechanism of micelles self-assembled from poly(ethylene glycol)-b-ploy(acrylic acid-co-acrylamidophenylboronic acid) PEG-b-P(AA-co-AAPBA) is deeply investigated.Different configurations of phenylboronic acid during various steps of glucose-responsive behaviors are clearly analyzed in the 11B 3Q MAS NMR spectra and coordination between carboxyl and PBA is confirmed.By increasing the AA units in PEG-b-P(AA-co-AAPBA),the carboxyl can coordinate with PBA moieties and cause the glucose-responsiveness of micelles even in the weak acid environment.
