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Chinese Chemical Letters 2022年第11期33卷 4948-4951页

作者： Lingyu Hang Chengying Shen Baode shen Hailong Yuan Department of Pharmacy Air Force Medical CenterPLABeijing 100142China College of Pharmacy Jiangxi University of Chinese MedicineNanchang 330004China Department of Pharmacy Jiangxi Provincial People's HospitalNanchang 330006China

Intravenous nanosuspensions are attracted growing attention as a viable strategy for development of intravenous formulations of poorly water-soluble drugs.However,only few information about the biological fate of intravenous nanosuspensions is currently known,especially amorphous nanosuspensions are not reported yet.In this study,the in vivo fate of herpetrione(HPE)amorphous nanosuspensions following intravenous administration was explored by using an aggregation-caused quenching(ACQ)probe and HPLC methods.The ACQ probe is physically embedded into HPE nanoparticles via anti-solvent method to form HPE hybrid nanosuspensions(HPE-HNSs)for bioimaging.HPE-HNSs emit strong and stable fluorescence,but fluorescence quenches immediately upon the dissolution of HPE-HNSs,confirming the selfdiscrimination of HPE-HNSs.Following intravenous administration of HPE-HNSs,integral HPE-HNSs and HPE show similar degradation and biodistribution,with rapid clearance from blood circulation and obvious accumulation in liver and lung.Due to the slower dissolution and enhanced recognition by reticuloendothelial system,450 nm HPE-HNSs accumulate more in liver,lung and spleen than that of 200 nm HPE-HNSs.These results demonstrate that integral HPE-HNSs determine the in vivo performance of HPEHNSs.This study provides insight into the in vivo fate of intravenous amorphous nanosuspensions.

关键词： Amorphous nanosuspensions Herpetrione In vivo fate Intravenous delivery Aggregation-caused quenching

The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin

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Acta Pharmaceutica Sinica B 2021年第4期11卷 978-988页

作者： Baode shen Chengying Shen Weifeng Zhu Hailong Yuan Department of Pharmacy Air Force Medical CenterPLABeijing 100142China Key Lab of Modern Preparation of Traditional Chinese Medicine(TCM) Ministry of EducationJiangxi University of TCMNanchang 330004China

In this study,self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals(QT-HNCs)with diameter around 280 nm(QT-HNCs-280)and550 nm(QT-HNCs-550)following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver.Results showed that QT-HNCs could reside in vivo as intact nanocrystals for as long as 48 h following oral and intravenous administration.A higher accumulation of integral QT-HNCs in liver and lung was observed for both oral and intravenous administration of QT-HNCs.The particle size affects the absorption and biodistribution of integral QT-HNCs and total QT.As compared to QT-HNCs-550,QT-HNCs-280 with smaller particle size is more easily absorbed,but dissolves faster in vivo,leading to higher distribution of QT(146.90 vs.117.91 h·mg/mL)but lower accumulation of integral nanocrystals(6.82 e10 vs.15.27 e10 h·[p/s]/[μW/cm2])in liver following oral administration.Due to its slower dissolution and enhanced recognition by RES,QT-HNCs-550 with larger diameter shows higher liver distribution for both of QT(1015.80 h·mg/mL)and integral nanocrystals(259.63 e10 h·[p/s]/[μW/cm2])than those of QT-HNCs-280(673.82&77.66 e10 h·[p/s]/[μW/cm2])following intravenous administration.The absolute exposure of integral QT-HNCs in liver following oral administration of QT-HNCs are 8.78%for QT-HNCs-280 and 5.88%for QT-HNCs-550,while the absolute exposure of total QT for QT-HNCs-280 and QT-HNCs-550 are 21.80%and 11.61%,respectively.Owing to imprecise quantifcation method,a surprisingly high contribution of integral QT-HNCs to oral bioavailability enhancement of QT(40.27%for QT-HNCs-280 and 50.65%for QT-HNCs-550)was obtained.These results revealed signifcant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intravenous administration of QT-HNCs,and provided a

关键词： Nanocrystals Biological fate Quercetin Pharmacokinetics Biodistribution Oral bioavailability Contribution Drug delivery

Effects of novel Fufang Biejia Ruangan Tablets with sheep placenta as substitute for Hominis Placenta on CCl4-induced liver fibrosis

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Chinese Herbal Medicines 2022年第1期14卷 104-110页

作者： Baode shen Li Deng Yuan Liu Ruisheng Li Chengying Shen Xiao Liu Yinchao Li Hailong Yuan Department of Pharmacy Air Force Medical CenterPLABeijing 100142China College of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Research Center for Clinical and Translational Medicine The Fifth Medical Center of ChinesePLA General HospitalBeijing 100039China School of Chemistry Biology and Material ScienceEast China University of TechnologyNanchang 330013China

Objective:Fufang Biejia Ruangan Tablet(FBRT) is widely used for the treatment of liver fibrosis.However,Hominis Placenta(HP),as an important adjuvant of FBRT,has been restricted for medicinal using due to the limited availability,ethical controversy and safety issues.The present study aimed to investigate the therapeutic effects of novel FBRT(N-FBRT) with sheep placenta(SP) as substitute for HP on liver fibrosis and explore its possible mechanisms.Different dosages of SP in N-FBRT were also evaluated.Methods:Rats were subcutaneously injected with CCl_(4)to induce liver fibrosis and then treated with NFBRT and FBRT.The anti-hepatic fibrosis effect was determined based on biomarkers analysis of liver function and hepatic fibrosis,and the liver pathology was visualized by H&E staining and Masson staining.The oxidative stress and inflammatory cytokines were also detected.Immunohistochemical staining of a-SMA,real time PCR and Western blotting were performed to evaluate hepatic stellate cells(HSCs)activation and TGF-β1/Smad signaling pathway.Results:N-FBRT and FBRT could ameliorate CCl_(4)-induced liver fibrosis and improve liver function,as evidenced by lowering serum biomarkers levels of liver function and hepatic fibrosis,and decreasing hepatic Hyp content and collagen deposition,and improving the hepatic morphology and architecture changes.Moreover,the anti-liver fibrosis effect was better when the dosage of SP used in N-FBRT was 1/2 of HP in FBRT.Administration of N-FBRT markedly alleviated oxidative stress and inflammatory cytokines,and inhibited a-SMA expression.Furthermore,the mRNA expression of Col Ⅰ,Col Ⅲ,a-SMA and TGF-β1,and proteins expression of a-SMA,TGF-β1,Smad2/3 and p-Smad2/3 were significantly down-regulated by N-FBRT treatment.Conclusion:SP can be used as substitute for HP to prepare N-FBRT for the treatment of liver fibrosis and the anti-liver fibrosis effect of N-FBRT is achieved by eliminating oxidative stress and inflammation,and inhibiting HSCs activation and ECM production by blocking TGF-β1/S

关键词： Fufang Biejia Ruangan Tablet Hominis Placenta liver fibrosis sheep placenta substitute TGF-β1/Smad signaling pathway

In vivo dissolution of poorly water-soluble drugs:Proof of concept based on fluorescence bioimaging

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Acta Pharmaceutica Sinica B 2021年第4期11卷 1056-1068页

作者： Yinqian Yang Yongjiu Lv Chengying Shen Tingting Shi Haisheng He Jianping Qi Xiaochun Dong Weili Zhao Yi Lu Wei Wu Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghai 201203China Center for Medical Research and Innovation Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China

In vitro-in vivo correlation(IVIVC)of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients.Nevertheless,in vivo dissolution profles have never been accurately portrayed.The current practice of IVIVC has to resort to in vivo absorption fractions(Fa).In this proof-of-concept study,in vivo dissolution of a model poorly watersoluble drug fenofbrate(FNB)was investigated by fuorescence bioimaging.FNB crystals were frst labeled by near-infrared fuorophores with aggregation-caused quenching properties.The dyes illuminated FNB crystals but quenched immediately and absolutely once been released into aqueous media,enabling accurate monitoring of residual drug crystals.The linearity established between fuorescence and crystal concentration justifed reliable quantifcation of FNB crystals.In vitro dissolution was frst measured following pharmacopoeia monograph protocols with well-documented IVIVC.The synchronicity between fuorescence and in vitro dissolution of FNB supported using fuorescence as a measure for determination of dissolution.In vitro dissolution correlated well with in vivo dissolution,acquired by either live or ex vivo imaging.The newly established IVIVC was further validated by correlating both in vitro and in vivo dissolution with Faobtained from pharmacokinetic data.

关键词： In vivo dissolution Fenofibrate Fluorescence Aggregation-caused quenching Bioimaging IVIVC

Daily administration times of Canhuang tablet based on a pharmacodynamic/pharmacokinetic model in jaundiced rats

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Journal of Traditional Chinese Medicine 2015年第1期35卷 84-89页

作者： Bai Jinxia Han Jin Chen Hongge shen Baode Xu He Dai Ling shen chengying Yuan Hailong Department of Pharmacy 302 Hospital of PLA Pharmacy College Chengdu University of Traditional Chinese Medicine

OBJECTIVE: To study the daily administration times of Canhuang tablet(CHT) for treating jaundice in rats based on a pharmacodynamic/ pharmacokinetic model.METHODS: Rats were modeled by 4% 1-Naphthylisothiocyanate(75 mg/kg, p.o.). After 48 h, CHT was given(p.o.) at 0.75 g/kg once a day, 0.375 g/kg twice a day, and 0.25 g/kg three times a day. Blood was collected from the orbital sinus at different intervals. Levels of liver enzymes and bilirubin were detected using these blood samples. Bile was collected and determined after the first administration of CHT. High-performance liquid chromatography was used to determine the concentration of berberine in bile simultaneously. Time-effect and time-dose curves were then obtained.RESULTS: Compared with rats taking CHT twiceand three times a day, the total amount of bile within 10 h of rats taking CHT once a day were 1.32-and 1.47-fold higher, respectively. There was good consistency between the pharmacokinetics of berberine and the pharmacodynamics of the effect on liver enzymes and bilirubin in vivo. The pharmacokinetic analyses showed that rats administered CHT once daily maintained a higher concentration of berberine in bile for a longer period than rats administered CHT two- and three-times daily.CONCLUSION: In jaundiced rats, taking CHT once a day is better than taking CHT twice or three times a day. These data may provide a reference for the clinical application of CHT.

关键词：动力学模型时间间隔日常管理药效学大鼠黄疸平板电脑高效液相色谱法

The Construction of the Major Clusters in Higher Vocational Colleges from the Perspective of Industrial Cluster

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International Journal of Technology Management 2015年第9期 14-16页

作者： Qingtang ZHANG Chengying Shen Jiangyin Polytechnic College Jiangyin 214405 Jiangsu China

Rational Daily Administration Times of Canhuang Tablet Based on PD/PK Model in Rats with Jaundice

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Rational Daily Administration Times of Canhuang Tablet Based...

第十四届全国中药和天然药物学术研讨会

作者： Jinxia Bai Jin Han Hongge Chen Baode shen He Xu Ling Dai Chengying Shen Hailong Yuan 302 Hospital of PLA

Objective To study the rational daily administration times of Canhuang Tablet(CHT) for treating jaundice in rats based on pharmacodynamics/ pharmacokinetics model.Methods Rats were mbdeled by orally administrating 4%1-Naphthylisothiocyanate(75mg/kg).After48 h,CHT was orally administrated with a dose of 0.75g/kg once a day,0.375 g/kg twice a day and 0.25 g/kg three times a day,respectively.Blood was collected from the orbital sinus at different intervals,then we investigated the levels of liver enzymes and bilirubins using these processed blood sample.Bile was collected and determined after first administration,and HPLC were used to determine the concentration of berberine in the bile at the same time.Finally,we obtained the time-effect curve and time-dose curve.Results Compared with the groups of rats taking CHT twice and thrice a day,the total bile within 10 h of the rats taking CHT once a day were 1.32 and 1.47 times higher,respectively.The results also showed that there was good consistency between pharmacokinetics of berberine and the pharmacodynamics of the effect on liver enzymes and bilirubins in vivo.AUC of berberine and the cholaneresis and retro-jaundice kinectics when administrated once a day were significantly higher than that of administrated 2 and 3 times a day.Conclusions It is reasonable to take CHT one time a day in the treatment of experimental jaundice,which may provide a reference for clinical application of CHT.

关键词： daily administration times Canhuang Tablet berberine Bile pharmacokinetics jaundice

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基于工程实践的污水处理教学平台设计

电子技术（上海） 2022年第3期51卷 230-231页

作者：徐娜沈澄英江阴职业技术学院江苏214405

阐述教学平台在污水处理工程实践中的应用,提出创新解决方法,包括理论与实践融合、工艺流程为主线,从而实现知识体系模块化、教学手段多样化、教学评价多面化。

关键词：创新教学工程实践知识体系教学平台

双地埋管群太阳能-地源热泵系统耦合方式研究

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太阳能学报 2020年第10期41卷 361-368页

作者：沈海笑王恩宇沈云祥齐承英河北工业大学能源与环境工程学院天津300401

针对天津地区办公建筑的负荷特点提出2种双地埋管群太阳能-地源热泵耦合系统(区别为供热季的太阳能直供或储热),进行为期20 a的模拟预测,得出2种系统的最佳运行工况,并对其运行性能和经济性进行分析。结果表明:从运行性能方面看,直供系... 详细信息

针对天津地区办公建筑的负荷特点提出2种双地埋管群太阳能-地源热泵耦合系统(区别为供热季的太阳能直供或储热),进行为期20 a的模拟预测,得出2种系统的最佳运行工况,并对其运行性能和经济性进行分析。结果表明:从运行性能方面看,直供系统运行20 a的平均系统COP可达3.78,比储热系统高5.3%;从追加投资费用和运行费用两方面考察二者的经济性,系统运行20 a直供系统比储热系统少花费0.52万元。

关键词：太阳能地源热泵经济性分析运行费用性能系数地埋管

Phospholipid-bile salts-mixed micelles incorporated in oral fast dissolving films for improving the oral bioavailability of poorly water soluble drugs

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Phospholipid-bile salts-mixed micelles incorporated in oral ...