Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
The new method proposed is based on the formation of hydralazine-Bromophenol blue ion pair simply and without further extraction or heating. The ion pair was prepared in the presence of pH 3 citrate buffer forming a y...The new method proposed is based on the formation of hydralazine-Bromophenol blue ion pair simply and without further extraction or heating. The ion pair was prepared in the presence of pH 3 citrate buffer forming a yellow-colored chromogen. A new maximum UV-visible band formed at 416 nm. The color was stable for more than 10 hours and obeyed Beer’s Law over the concentration range of 10 - 50 µg/mL. The calculated molar absorptivity and Sandell’s sensitivity were 1.01 × 104 L∙mol−1∙cm−1 and 0.0514 µg/mL, respectively. The elements of method validation stipulated by The International Conference on Harmonization [Q2 (R1)] were applied for hydralazine hydrochloride assay in pure and pharmaceutical tablet formulation. The average recoveries of the pure solution and the pharmaceutical formulation were 98.94% and 99.50%, respectively. The results were statistically compared by F-test, which indicates that the method can be precise and repeatable for both pure and pharmaceutical solutions. The method was found to be accurate, reproducible, and cost-effective, and validated for the assay of hydralazine in terms of the routine quality control.展开更多
Two simple and rapid analytical methods (DSC and <sup>1</sup>H-NMR), are proposed for determination of meclofenoxate in meclofenoxate hydrochloride for injection. DSC thermogram is recorded without any sam...Two simple and rapid analytical methods (DSC and <sup>1</sup>H-NMR), are proposed for determination of meclofenoxate in meclofenoxate hydrochloride for injection. DSC thermogram is recorded without any sample pretreatment. The response linearity is ensured by linear determination factors R<sup>2</sup>, which is 0.9982. The recoveries of meclofenoxate hydrochloride in sterile powder for injection are from 98.3% to 102.3% (n = 3). The quantitative <sup>1</sup>H-NMR is quick and simple to use. The quantitation of meclofenoxate is reproducible and the relative standard deviation is 1.0%. The accuracy of two methods is validated by comparison with the results obtained by HPLC. The results show that the two methods are capable of quantifying the content of meclofenoxate in meclofenoxate hydrochloride for injection.展开更多
Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine h...Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine hydrochloride yield. In this study, a new purification process for sinomenine hydrochloride was proposed by using the extract obtained from acid extraction of Caulis Sinomenii as the starting material.The process included the following steps: alkalization, extraction, water washing, acid–water stripping,drying, and crystallization. 1-Heptanol was used as the extractant. The distribution coefficients of sinomenine and sinomenine hydrochloride in 1-heptanol–water system were 27.4 and 0.0167, respectively.The dissociation constants of sinomenine hydrochloride were 8.27 and 11.24, respectively. Process parameters of the new purification process were optimized with experimental design. The extractant1-heptanol and sinomenine hydrochloride in the crystallization mother solution can be recycled in the new process. The purity of the obtained sinomenine hydrochloride crystals exceeded 85%, and the yield was about 70%. Compared with current industrial processes, safer extractant, less solid waste, and higher sinomenine hydrochloride yield can be achieved using the new purification process of sinomenine hydrochloride provided in this study.展开更多
The aim of this study is to investigate the pharmacokinetics of 5′-valyl-cytarabine hydrochloride(OPC) when co-administered with cephalexin, which are both the substrates of PepT 1.The drugs were administered orally ...The aim of this study is to investigate the pharmacokinetics of 5′-valyl-cytarabine hydrochloride(OPC) when co-administered with cephalexin, which are both the substrates of PepT 1.The drugs were administered orally by gavage. Blood samples were collected from the orbital plexus of the rats after oral administration of drug solutions. A new high-performance liquid chromatographic method was validated and used for determination of the two drugs. Pharmacokinetic parameters were calculated using DAS 2.1.1 software with noncompartmental analysis. After oral administration of OPC and co-administration of OPC and cephalexin,there were significant differences in the main pharmacokinetic parameters. The main pharmacokinetic parameters for the OPC group and the co-administrative group were as follows:AUC0-10(18,168.7 ± 2561.4) ng·h/ml and(13,448.5 ± 2544.73) ng·h/ml, AUC0-∞(18,683.1 ± 3066.5)ng·h/ml and(13,721.1 ± 2683.0) ng·h/ml, Cmax(6654.8 ± 481.3) ng/ml and(4765.1 ± 928.9) ng/ml, respectively. The results showed that the bioavailability of OPC could be reduced when co-administered with cephalexin, suggesting that the efficacy of a novel drug might be reduced when it came to combination use of β-lactam antibiotics.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
文摘The new method proposed is based on the formation of hydralazine-Bromophenol blue ion pair simply and without further extraction or heating. The ion pair was prepared in the presence of pH 3 citrate buffer forming a yellow-colored chromogen. A new maximum UV-visible band formed at 416 nm. The color was stable for more than 10 hours and obeyed Beer’s Law over the concentration range of 10 - 50 µg/mL. The calculated molar absorptivity and Sandell’s sensitivity were 1.01 × 104 L∙mol−1∙cm−1 and 0.0514 µg/mL, respectively. The elements of method validation stipulated by The International Conference on Harmonization [Q2 (R1)] were applied for hydralazine hydrochloride assay in pure and pharmaceutical tablet formulation. The average recoveries of the pure solution and the pharmaceutical formulation were 98.94% and 99.50%, respectively. The results were statistically compared by F-test, which indicates that the method can be precise and repeatable for both pure and pharmaceutical solutions. The method was found to be accurate, reproducible, and cost-effective, and validated for the assay of hydralazine in terms of the routine quality control.
文摘Two simple and rapid analytical methods (DSC and <sup>1</sup>H-NMR), are proposed for determination of meclofenoxate in meclofenoxate hydrochloride for injection. DSC thermogram is recorded without any sample pretreatment. The response linearity is ensured by linear determination factors R<sup>2</sup>, which is 0.9982. The recoveries of meclofenoxate hydrochloride in sterile powder for injection are from 98.3% to 102.3% (n = 3). The quantitative <sup>1</sup>H-NMR is quick and simple to use. The quantitation of meclofenoxate is reproducible and the relative standard deviation is 1.0%. The accuracy of two methods is validated by comparison with the results obtained by HPLC. The results show that the two methods are capable of quantifying the content of meclofenoxate in meclofenoxate hydrochloride for injection.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202002)the National Project for Standardization of Chinese Materia Medica (ZYBZH-C-GD-04)。
文摘Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine hydrochloride yield. In this study, a new purification process for sinomenine hydrochloride was proposed by using the extract obtained from acid extraction of Caulis Sinomenii as the starting material.The process included the following steps: alkalization, extraction, water washing, acid–water stripping,drying, and crystallization. 1-Heptanol was used as the extractant. The distribution coefficients of sinomenine and sinomenine hydrochloride in 1-heptanol–water system were 27.4 and 0.0167, respectively.The dissociation constants of sinomenine hydrochloride were 8.27 and 11.24, respectively. Process parameters of the new purification process were optimized with experimental design. The extractant1-heptanol and sinomenine hydrochloride in the crystallization mother solution can be recycled in the new process. The purity of the obtained sinomenine hydrochloride crystals exceeded 85%, and the yield was about 70%. Compared with current industrial processes, safer extractant, less solid waste, and higher sinomenine hydrochloride yield can be achieved using the new purification process of sinomenine hydrochloride provided in this study.
基金financially supported by the National Nature Science Foundation of China (No.81302722)
文摘The aim of this study is to investigate the pharmacokinetics of 5′-valyl-cytarabine hydrochloride(OPC) when co-administered with cephalexin, which are both the substrates of PepT 1.The drugs were administered orally by gavage. Blood samples were collected from the orbital plexus of the rats after oral administration of drug solutions. A new high-performance liquid chromatographic method was validated and used for determination of the two drugs. Pharmacokinetic parameters were calculated using DAS 2.1.1 software with noncompartmental analysis. After oral administration of OPC and co-administration of OPC and cephalexin,there were significant differences in the main pharmacokinetic parameters. The main pharmacokinetic parameters for the OPC group and the co-administrative group were as follows:AUC0-10(18,168.7 ± 2561.4) ng·h/ml and(13,448.5 ± 2544.73) ng·h/ml, AUC0-∞(18,683.1 ± 3066.5)ng·h/ml and(13,721.1 ± 2683.0) ng·h/ml, Cmax(6654.8 ± 481.3) ng/ml and(4765.1 ± 928.9) ng/ml, respectively. The results showed that the bioavailability of OPC could be reduced when co-administered with cephalexin, suggesting that the efficacy of a novel drug might be reduced when it came to combination use of β-lactam antibiotics.
