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

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 *** 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 *** particle size affects the absorption and biodistribution of integral QT-HNCs and total *** 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 *** 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 *** 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%,*** 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 *** results revealed signifcant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intr

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

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Insight into the in vivo fate of intravenous herpetrione amorphous nanosuspensions by aggregation-caused quenching probes

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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 ***,only few information about the biological fate of intravenous nanosuspensions is currently known,especially amorphous nanosuspensions are not reported *** 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 *** ACQ probe is physically embedded into HPE nanoparticles via anti-solvent method to form HPE hybrid nanosuspensions(HPE-HNSs)for ***-HNSs emit strong and stable fluorescence,but fluorescence quenches immediately upon the dissolution of HPE-HNSs,confirming the selfdiscrimination of *** 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 *** 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 *** results demonstrate that integral HPE-HNSs determine the in vivo performance of *** 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

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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 ***: 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 ***: 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 ***: 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： Jaundice 1-Naphthylisothiocyanate Pharmacokinetics Berberine Pharmacology Can-huang tablet

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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 ***,Hominis Placenta(HP),as an important adjuvant of FBRT,has been restricted for medicinal using due to the limited availability,ethical controversy and safety *** 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 *** dosages of SP in N-FBRT were also ***:Rats were subcutaneously injected with CCl_(4)to induce liver fibrosis and then treated with NFBRT and *** 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 *** oxidative stress and inflammatory cytokines were also *** staining of a-SMA,real time PCR and Western blotting were performed to evaluate hepatic stellate cells(HSCs)activation and TGF-β1/Smad signaling ***: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 ***,the anti-liver fibrosis effect was better when the dosage of SP used in N-FBRT was 1/2 of HP in *** of N-FBRT markedly alleviated oxidative stress and inflammatory cytokines,and inhibited a-SMA ***,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 ***: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 ac

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

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

Rational Daily Administration Times of Canhuang Tablet Based...

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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 *** 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,*** was collected from the orbital sinus at different intervals,then we investigated the levels of liver enzymes and bilirubins using these processed blood *** was collected and determined after first administration,and HPLC were used to determine the concentration of berberine in the bile at the same ***,we obtained the time-effect curve and time-dose *** 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,*** results also showed that there was good consistency between pharmacokinetics of berberine and the pharmacodynamics of the effect on liver enzymes and bilirubins in *** 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 *** 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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Nanosuspensions of Poorly Water Soluble Drugs Prepared by Precipitation-Combined Homogenization Technology based on Acid-Base Neutralization Reactions

Nanosuspensions of Poorly Water Soluble Drugs Prepared by Pr...

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2015年中国药学大会暨第十五届中国药师周

作者： Gang shen Ling Cheng Lihong Zhang baode shen Juanjuan Li Juan Zhen Rong Xu Hailong Yuan Pharmacy College Chengdu University of Traditional Chinese Medicine Department of Pharmacy Air Force General Hospital of PLA

Herpetospermum caudigerum lignans（HTL）, one of the potential drugs with the treatment of anti-hepatitis B virus and hepatoprotective effects, have been limited in clinical applications because of poor saturation solubility, resulting in low bioavailability. Both herpetrione（HPE） and herpetin（HPN） are considered as the most abundant ingredient in HTL and exhibit weak acidity. The purpose of this study was to produce dried preparations of HTL（composed of HPE and HPN） nosuspensions with high redispersibility using lyophilization. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and variously critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, physical stability, solubility, dissolution and bioavailability. The dried preparations with a mean redispersed particle size of 286 nm was produced by using 4%（w/v） mannitol as cryoprotectants and possessed good physical stability at 4 oC or 25 oC for two months. Meanwhile, in vitro evaluation showed dried preparations could significantly increase saturation solubility and dissolution rate along with improving in vivo oral bioavailability, when compared with raw drug. This study provides a feasible drug delivery system for poorly water-soluble ingredients with pH-dependent solubility.

关键词： Herpetospermum caudigerum lignans nanosuspensions acid–base neutralization saturation solubility dissolution oral bioavailability

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Development and characterization of mucoadhesive buccal films containing phospholipid-bile salts-mixed micelles for Cucurbitacin B delivery

Development and characterization of mucoadhesive buccal film...

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2013年中国药学大会暨第十三届中国药师周

作者： Qingyuan Lv Chengying shen Xianyi Li baode shen Chao Yu Pinghua Xu He Xu Jin Han Hailong Yuan Department of Pharmacy 302 Military Hospital Institute for Drug and Instrument Control Health Department GLD of PLA

Cucurbitacin B （Cu B）, a potent anti-cancer agents, suffers with the problems of gastrointestinal side effects and non-specific toxicity via oral administration and drawbacks in patients compliance and acceptance through injections. An integration of nanoscopic carriers with mucoadhesive buccal films drug delivery system would resolve these issues effectively with greater therapeutic benefits and clinical significance. Thus, the drug loaded mucoadhesive buccal film was developed and characterized in this study and the carboxymethyl chitosan （CCS） was choosed as a bioadhesive polymer, glycerol was choosed as a plasticizer and phospholipid-bile salts-mixed micelles （PL-BS-MMs） was selected as the nanoscopic carriers. The CCS-films containing Cu B loaded PL/SDC-MMs was evaluted for the mechanical properties, mucoadhesion properties, in vitro water-uptake, in vitro release and morphological properties, respectively. The optimal CCS-films containing Cu B loaded PL/SDC-MMs was easily reconstituted in a transparent and clear solution giving back a colloidal system with spherical micelles in the submicron range and presenting the good characteristics after reconstituting into micelles solution compared with corresponding results of initial Cu B-PL/SDC-MMs solution. The in vivo study revealed a greater and more extended release of Cu B from nanoscopic CCS-films compared to that from a conventional CCS films （C-CCS-films） and oral marketed tablet （Hulusupian）. The AUC 0-36h for CCS-films containing Cu B loaded PL/SDC-MMs was found to be 46.43±5.11 μg/mL/h in comparison to 4.44±1.21 μg/mL/h and 17.23±3.46 μg/mL/h for C-CCS-films and oral tablet, respectively. The absorption of Cu B from CCS-films containing Cu B loaded PL/SDC-MMs resulted in 2.69-fold increased in bioavailability as compared to conventional tablet formulation and 10.46 times with reference to the C-CCS-films formulation. Thus, this kind of mucoadhesive buccal film might be an alternative safe route for deliver

关键词： Cucurbitacin B phospholipid-bile salts-mixed micelles film carboxymethyl chitosan bioavailability

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

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

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“好医生杯”中药制剂创新与发展论坛

作者： Qingyuan Lv Minggui Lin Chao Yu baode shen He Xu Chengying shen Ling Dai Hailong Yuan Jin Han Department of Pharmacy 302 Military Hospital Institute of Tuberculosis 309 Military Hospital

The phospholipid-bile salts-mixed micelles(PL-BS-MMs)are potent carriers used for oral absorption of drugs that are poorly soluble in water;however,there are many limitations associated with liquid *** the current study,the feasibility of preparing a solid PL-BS-MMs by incorporating liquid PL/SDC-MMs with solid fast dissolving oral films(FDOFs)carriers was *** incorporated with Cucurbitacin B(Cu B)loaded PL-BS-MMs have been developed and *** were produced by solvent casting *** formulation presenting the best characteristics before solidifying and after *** containing Cu B loaded PL/SDC-MMs was easily reconstituted in a transparent and clear solution giving back a colloidal system with spherical micelles in the submicron *** pharmacokinetics study showed that the FDOFs containing PL/SDC-MMs not only kept the absorption properties as same as liquid PL/SDC-MMs,but also significantly increased the oral bioavailability of Cu B compared to the Cu B solution(p<0.05).This study showed that the solid PL/SDC-MMs based on FDOFs could represent a novel platform for the delivery of poorly water soluble drugs via oral ***,the integration with the FDOFs could also provide a simple and cost-effective manner for the solidification of PL/SDC-MMs.

关键词： Cucurbitacin B phospholipid-bile salts-mixed micelles fast dissolving oral films oral bioavailability poorly water soluble drugs

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立方液晶作为天然药物载体的研究进展

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中国医药工业杂志 2018年第11期49卷 1500-1507页

作者：徐玲霞申宝德金晨朱卫丰江西中医药大学现代中药制剂教育部重点实验室江西南昌330004

通过以"立方液晶"、"非层状液晶"、"cubosomes"、"cubic liquid crystalline"等为关键词,组合查询PubMed、中国知网、维普和万方数据库中有关于立方液晶的形成机制、相转变影响因素及作为天然药物载体研究的相关文献并进行综述,以期为... 详细信息

通过以"立方液晶"、"非层状液晶"、"cubosomes"、"cubic liquid crystalline"等为关键词,组合查询PubMed、中国知网、维普和万方数据库中有关于立方液晶的形成机制、相转变影响因素及作为天然药物载体研究的相关文献并进行综述,以期为立方液晶递送系统的深入研究与发展提供借鉴与思考。

关键词：立方液晶形成机制相转变天然药物

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pH依赖的溶解/沉淀法制备美洛昔康纳米混悬剂

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中国医药工业杂志 2018年第2期49卷 192-197页

作者：连王权申宝德沈成英徐方楚袁海龙江西中医药大学药学院江西南昌330004 空军总医院北京100142

为提高美洛昔康(1)的溶出度,采用p H依赖的溶解/沉淀法制备其纳米混悬剂。以1纳米混悬剂的平均粒径、多分散性指数(PDI)及稳定性为指标,采用单因素法优化其处方和工艺。所得最优处方和工艺为:使用泊洛沙姆407(P407)和Tween-80(T80)(1∶1... 详细信息

为提高美洛昔康(1)的溶出度,采用p H依赖的溶解/沉淀法制备其纳米混悬剂。以1纳米混悬剂的平均粒径、多分散性指数(PDI)及稳定性为指标,采用单因素法优化其处方和工艺。所得最优处方和工艺为:使用泊洛沙姆407(P407)和Tween-80(T80)(1∶1,w/w)作1纳米混悬剂的稳定剂,用量与主药1的比例为1∶2(w/w);以13 000 r/min的速率高速剪切2 min。验证试验显示,3批1纳米混悬剂的平均粒径均在200 nm以内,PDI值约0.2;室温放置7 d后,平均粒径的波动在30 nm内,PDI波动在0.03以内。采用扫描电镜对其形态进行观察,结果显示1纳米混悬剂呈不规则的椭圆形小颗粒,表面光滑。体外溶出度显示,1纳米混悬剂在磷酸盐缓冲液(p H 7.4)中5 min即可溶出(91.68±3.26)%,而1粗混悬液60 min时溶出率仅为(50.45±3.13)%。结果表明将1制成纳米混悬剂后,其溶出度得到显著改善。

关键词：美洛昔康纳米混悬剂 pH依赖的溶解/沉淀法溶出度

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