目的观察扶正解毒化瘀方总苷提取物对呼吸道合胞病毒(RSV)感染HEp-2细胞Toll样受体(TLRs)相关细胞炎性因子的影响,探讨其可能的作用机制。方法建立RSV感染HEp-2细胞模型,随机分为病毒对照组、总苷提取物组及利巴韦林组,各给药组给予相...目的观察扶正解毒化瘀方总苷提取物对呼吸道合胞病毒(RSV)感染HEp-2细胞Toll样受体(TLRs)相关细胞炎性因子的影响,探讨其可能的作用机制。方法建立RSV感染HEp-2细胞模型,随机分为病毒对照组、总苷提取物组及利巴韦林组,各给药组给予相应药物,同时以未感染RSV的HEp-2细胞作为空白对照。应用液相色谱-质谱分析扶正解毒化瘀方全方、总苷提取物及其药物血清的主要成分。采用ELISA检测细胞上清液白细胞介素(IL)-1β、IL-8、干扰素-α(IFN-α)、TLR3、TLR7水平。结果扶正解毒化瘀方全方提取物共鉴别出10个化学成分,以苷类为主。扶正解毒化瘀方总苷提取物共鉴别出9个化学成分,其中入血成分共鉴别出8个化学成分,包括芍药苷、木犀草素、野黄芩苷、连翘酯苷H、异荭草苷、连翘苷、人参皂苷Rb1、人参皂苷Re。与HEp-2细胞组比较,病毒对照组感染后24、48、72 h IFN-α、IL-1β、IL-8、TLR3和TLR7水平均升高;与病毒对照组比较,总苷提取物组感染后24、48、72 h IFN-α、IL-1β、IL-8、TLR3和TLR7水平均降低。结论扶正解毒化瘀方总苷提取物可能通过调节TLRs相关细胞炎性因子,抑制细胞炎性反应起到治疗RSV肺炎的作用。展开更多
目的探究重症患者应用万古霉素联合哌拉西林他唑巴坦(VPT)与万古霉素联合美罗培南(VM)、万古霉素联合氨曲南(VA)、万古霉素联合头孢哌酮舒巴坦(VCS)之间急性肾损伤(AKI)发生率及临床预后的差异。方法回顾性研究2017年9月至2020年4月接受...目的探究重症患者应用万古霉素联合哌拉西林他唑巴坦(VPT)与万古霉素联合美罗培南(VM)、万古霉素联合氨曲南(VA)、万古霉素联合头孢哌酮舒巴坦(VCS)之间急性肾损伤(AKI)发生率及临床预后的差异。方法回顾性研究2017年9月至2020年4月接受VPT、VM、VA、VCS联合治疗至少48 h的重症患者病例,按联合使用的β-内酰胺类抗菌药物进行分组,收集各组临床资料,比较AKI发生率和临床预后。应用多因素Logistic回归对AKI发生的危险因素进行分析。结果共纳入133例病例,其中VPT组32例、VM组64例、VA+VCS组37例。AKI总发生率为22.56%。VPT组、VM组、VA+VCS组间AKI发生率差异有统计学意义(40.63% vs 17.19% vs 16.22%,P<0.05)。三组间肾脏替代治疗率、院内病死率差异无统计学意义(P>0.05)。多因素Logistic回归分析发现,应用VPT(OR=3.324,95%CI:1.266~8.733,P=0.015)、万古霉素谷浓度增加(OR=1.066,95%CI:1.018~1.116,P=0.006)和急性生理与慢性健康评估Ⅱ(APACHE-Ⅱ)评分升高(OR=1.110,95%CI:1.027~1.200,P=0.009),是重症患者发生AKI的独立危险因素。结论重症患者应用万古霉素联合VPT治疗出现AKI风险高于联合VM、VA与VCS,需要谨慎用药。展开更多
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 com...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.展开更多
文摘目的观察扶正解毒化瘀方总苷提取物对呼吸道合胞病毒(RSV)感染HEp-2细胞Toll样受体(TLRs)相关细胞炎性因子的影响,探讨其可能的作用机制。方法建立RSV感染HEp-2细胞模型,随机分为病毒对照组、总苷提取物组及利巴韦林组,各给药组给予相应药物,同时以未感染RSV的HEp-2细胞作为空白对照。应用液相色谱-质谱分析扶正解毒化瘀方全方、总苷提取物及其药物血清的主要成分。采用ELISA检测细胞上清液白细胞介素(IL)-1β、IL-8、干扰素-α(IFN-α)、TLR3、TLR7水平。结果扶正解毒化瘀方全方提取物共鉴别出10个化学成分,以苷类为主。扶正解毒化瘀方总苷提取物共鉴别出9个化学成分,其中入血成分共鉴别出8个化学成分,包括芍药苷、木犀草素、野黄芩苷、连翘酯苷H、异荭草苷、连翘苷、人参皂苷Rb1、人参皂苷Re。与HEp-2细胞组比较,病毒对照组感染后24、48、72 h IFN-α、IL-1β、IL-8、TLR3和TLR7水平均升高;与病毒对照组比较,总苷提取物组感染后24、48、72 h IFN-α、IL-1β、IL-8、TLR3和TLR7水平均降低。结论扶正解毒化瘀方总苷提取物可能通过调节TLRs相关细胞炎性因子,抑制细胞炎性反应起到治疗RSV肺炎的作用。
文摘目的探究重症患者应用万古霉素联合哌拉西林他唑巴坦(VPT)与万古霉素联合美罗培南(VM)、万古霉素联合氨曲南(VA)、万古霉素联合头孢哌酮舒巴坦(VCS)之间急性肾损伤(AKI)发生率及临床预后的差异。方法回顾性研究2017年9月至2020年4月接受VPT、VM、VA、VCS联合治疗至少48 h的重症患者病例,按联合使用的β-内酰胺类抗菌药物进行分组,收集各组临床资料,比较AKI发生率和临床预后。应用多因素Logistic回归对AKI发生的危险因素进行分析。结果共纳入133例病例,其中VPT组32例、VM组64例、VA+VCS组37例。AKI总发生率为22.56%。VPT组、VM组、VA+VCS组间AKI发生率差异有统计学意义(40.63% vs 17.19% vs 16.22%,P<0.05)。三组间肾脏替代治疗率、院内病死率差异无统计学意义(P>0.05)。多因素Logistic回归分析发现,应用VPT(OR=3.324,95%CI:1.266~8.733,P=0.015)、万古霉素谷浓度增加(OR=1.066,95%CI:1.018~1.116,P=0.006)和急性生理与慢性健康评估Ⅱ(APACHE-Ⅱ)评分升高(OR=1.110,95%CI:1.027~1.200,P=0.009),是重症患者发生AKI的独立危险因素。结论重症患者应用万古霉素联合VPT治疗出现AKI风险高于联合VM、VA与VCS,需要谨慎用药。
基金financially supported by National Natural Science Foundation of China(No.81173563)Ministry of National Science and Technology(China+2 种基金Nos.2012ZX09103201-0262009ZX09102-142)the Innovation Team of Beijing University of Chinese Medicine(No.2011-CXTD-13)
文摘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.
