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Exploring the utility of the Chasing Principle:influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

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Acta Pharmaceutica Sinica B 2019年第1期9卷 194-201页

作者： Scheyla Daniela Siqueira J?rgensen Thomas Rades Huiling mu Kirsten Graeser Anette müllertz Department of Pharmacy Faculty of Health and Medical Sciences University of Copenhagen Roche Pharma Research and Development Therapeutic Modalities Roche Innovation Center Basel

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol(CAR), cinnarizine(CIN) or R3040 on drug solubilization in a twocompartment in vitro lipolysis model. Correlation of drug log P or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:maisine 35-1(1:1, w/w) and Kolliphor RH40, with ethanol at 10%(w/w) were used. SNEDDS were named f65, f55 and f20(numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS(f0) were also analyzed. While the ranking order of drug solubilization was f65? f55? f204f0 for CAR; f65? f554f204f0 for CIN and f65? f55? f204f0 for R3040-with higher CAR solubilization than for R3040 and CIN-the ranking of S_(eq)of CAR, CIN and R3040 in SNEDDS was f65 o f55o f20, f65? f554f20 and f654f554f20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. furthermore, high S_(eq) in SNEDDS did not reflect high drug solubilization. As CAR(log P 3.8) showed higher solubilization than CIN(log P 5.8) and R3040(log P 10.4), a correlation between drug log P and drug solubilization was observed.

关键词： Self-nanoemulsiying drug delivery system(SNEDDS) Chasing principle Two-compartment in vitro lipolysis Rat gastrointestinal conditions Drug solubilization

Group B Streptococcal Chorioamnionitis with Intact Amniotic membranes. A Rare?

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Open Journal of Obstetrics and Gynecology 2020年第6期10卷 809-814页

作者： J. L. Gallo Vallejo C. Rodríguez-Rubio Corona m. f. Hurtado Sánchez A. Alkourdi martínez L. Revelles Paniza Obstetrics and Gynecology Service Virgen de las Nieves University Hospital Granada Spain

Group B streptococcus infection (GBS) is an important cause of perinatal infection. maternal colonization by GBS can cause amniotic infection and thus fetal infection, sometimes causing fetal death. This infection generally occurs in association with premature rupture of membranes. We present here an infrequent case of GBS chorioamnionitis in full-term gestation with intact amniotic membranes. The curiosity of the case lies in the integrity of the amniotic membranes, the asymptomatic clinical presentation, and the adverse result (term.f.tal death).

关键词： Chorioamnionitis Group B Streptococcus Intact Amniotic membranes

Luminosities and energies of e^(+)e^(−) collision data taken between √s=4.61 GeV and 4.95 GeV at BESⅢ

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Chinese Physics C 2022年第11期46卷 64-75页

作者： m.Ablikim m.N.Achasov P.Adlarson m.Albrecht R.Aliberti A.Amoroso m.R.An Q.An X.H.Bai Y.Bai O.Bakina R.Baldini ferroli I.Balossino Y.Ban V.Batozskaya D.Becker K.Begzsuren N.Berger m.Bertani D.Bettoni f.Bianchi J.Bloms A.Bortone I.Boyko R.A.Briere A.Brueggemann H.Cai X.Cai A.Calcaterra G.f.Cao N.Cao S.A.Cetin J.f.Chang W.L.Chang G.Chelkov C.Chen G.Chen H.S.Chen m.L.Chen S.J.Chen T.Chen X.R.Chen X.T.Chen Y.B.Chen Z.J.Chen W.S.Cheng X.Chu G.Cibinetto f.Cossio J.J.Cui H.L.Dai J.P.Dai A.Dbeyssi R.Ede Boer D.Dedovich Z.Y.Deng A.Denig I.Denysenko m.Destefanis f.De mori Y.Ding J.Dong L.Y.Dong m.Y.Dong X.Dong S.X.Du P.Egorov Y.L.fan J.fang S.S.fang W.X.fang Y.fang R.farinelli L.fava f.feldbauer G.felici C.Q.feng J.H.feng K fischer m.f.itsch C.fritzsch C.D.fu H.Gao Y.N.Gao Yang Gao S.Garbolino I.Garzia P.T.Ge C.Geng E.m.Gersabeck A Gilman K.Goetzen L.Gong W.X.Gong W.Gradl m.Greco m.H.Gu C.Y Guan A.Q.Guo L.B.Guo R.P.Guo Y.P.Guo A.Guskov T.T.Han W.Y.Han X.Q.Hao f.A.Harris K.K.He K.L.He f.H.Heinsius C.H.Heinz Y.K.Heng C.Herold m.Himmelreich T.Holtmann G.Y.Hou Y.R.Hou Z.L.Hou H.m.Hu J.f.Hu T.Hu Y.Hu G.S.Huang K.X.Huang L.Q.Huang L.Q.Huang X.T.Huang Y.P.Huang Z.Huang T.Hussain N Husken W.Imoehl m.Irshad J.Jackson S.Jaeger S.Janchiv Q.Ji Q.P.Ji X.B.Ji X.L.Ji Y.Y.Ji Z.K.Jia H.B.Jiang S.S.Jiang X.S.Jiang Y.Jiang J.B.Jiao Z.Jiao S.Jin Y.Jin m.Q.Jing T.Johansson N.Kalantar-Nayestanaki X.S.Kang R.Kappert m.Kavatsyuk B.C.Ke I.K.Keshk A.Khoukaz P.Kiese R.Kiuchi R.Kliemt L.Koch O.B.Kolcu B.Kopf m.Kuemmel m.Kuessner A.Kupsc W.Kuhn J.J.Lane J.S.Lange P.Larin A.Lavania L.Lavezzi Z.H.Lei H.Leithoff m.Lellmann T.Lenz C.Li C.Li C.H.Li Cheng Li D.m.Li f.Li G.Li H.Li H.Li H.B.Li H.J.Li H.N.Li J.Q.Li J.S.Li J.W.Li Ke Li L.J Li L.K.Li Lei Li m.H.Li P.R.Li S.X.Li S.Y.Li T.Li W.D.Li W.G.Li X.H.Li X.L.Li Xiaoyu Li Z.Y.Li H.Liang H.Liang H.Liang Y.f.Liang Y.T.Liang G.R.Liao L.Z.Liao J.Libby A.Limphirat C.X.Lin D.X.Lin T.Lin B.J.Liu C.X.Liu D.Liu f.H.Liu fang Liu feng Liu G.m.Liu H.Liu H.m.Liu Huanhuan Liu Huihui Liu J.B.Liu J.L.Liu J.Y.Liu K.Liu K.Y.L Institute of High Energy Physics Beijing 100049China Beihang University Beijing 100191China Beijing Institute of Petrochemical Technology Beijing 102617China Bochum Ruhr-University D-44780 BochumGermany Carnegie mellon University PittsburghPennsylvania 15213USA Central China Normal University Wuhan 430079China China Center of Advanced Science and Technology Beijing 100190China COmSATS University Islamabad Lahore CampusDefence RoadOff Raiwind Road54000 LahorePakistan fudan University Shanghai 200433China G.I.Budker Institute of Nuclear Physics SB RAS(BINP) Novosibirsk 630090Russia GSI Helmholtzcentre for Heavy Ion Research GmbH D-64291 DarmstadtGermany Guangxi Normal University Guilin 541004China Hangzhou Normal University Hangzhou 310036China Helmholtz Institute mainz Staudinger Weg 18D-55099 MainzGermany Henan Normal University Xinxiang 453007China Henan University of Science and Technology Luoyang 471003China Henan University of Technology Zhengzhou 450001China Huangshan College Huangshan 245000China Hunan Normal University Changsha 410081China Hunan University Changsha 410082China Indian Institute of Technology madras Chennai 600036India Indiana University BloomingtonIndiana 47405USA INfN Laboratori Nazionali di frascati INFN Laboratori Nazionali di FrascatiI-00044FrascatiItaly INfN Laboratori Nazionali di frascati INFN Sezione di PerugiaI-06100PerugiaItaly INfN Laboratori Nazionali di frascati University of PerugiaI-06100PerugiaItaly INfN Sezione di ferrara INFN Sezione di FerraraI-44122FerraraItaly INfN Sezione di ferrara University of FerraraI-44122FerraraItaly Institute of modern Physics Lanzhou 730000China Institute of Physics and Technology Peace Ave.54BUlaanbaatar 13330Mongolia Jilin University Changchun 130012China Johannes Gutenberg University of mainz Johann-Joachim-Becher-Weg 45D-55099 MainzGermany Joint Institute for Nuclear Research 141980 DubnaMoscow regionRussia Justus-Liebig-Universitaet Giessen II.Physikalisches InstitutHeinrich-Buff-Ring 16

from December 2019 to June 2021,the BESⅢ experiment collected approximately 5.85 fb^(−1) of data at center-of-mass energies between 4.61 and 4.95 *** is the highest collision energy BEPCⅡ has reached to *** accumulated e^(+)e^(−) annihilation data samples are useful for studying charmonium(-like)states and charmed-hadron *** adopting a novel method of analyzing the production of A_(c)^(+)A_(c)^(-) pairs in e^(+)e^(−) annihilation,the center-of-mass energies are measured with a precision of 0.6 *** luminosities are measured with a precision of better than 1% by analyzing the events of large-angle Bhabha *** measurements provide important inputs to analyses based on these data samples.

关键词： luminosity center-of-mass energy BESⅢdetector

时域反射谱法研究烷基丙烯酸酯与酚复合的介电弛豫(英文)

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物理化学学报 2007年第5期23卷 709-712页

作者： LIAKATH ALI KHAN f. SIVAGURUNATHAN P. mEHROTRA S. C. Annamalai University Annamalai Nagar Tamil Nadu-608 002 India Dr. B.A.m. University Aurangabad-431 004 Maharashtra India

The dielectric relaxation measurements on binary mixtures of esters (methyl acrylate, ethyl acrylate, and butyl acrylate) with phenol derivatives (p-cresol, p-chlorophenol, and 2,4-dichlorophenol) were carried out at different concentrations at 303 K using the time domain reflectometry (TDR) over the frequency range from 10 mHz to 20 GHz. The Kirkwood correlation factor and excess inverse relaxation time were determined and discussed to yield information on the molecular interactions of the systems. The relaxation time increased with increasing concentration of phenols and increasing chain length of esters. The excess inverse relaxation time values were negative for all the systems, which indicated the solute-solvent interaction existing between esters and phenols producing a field in such a way that the effective dipole rotation was hindered.

关键词：烷基丙烯酸盐苯酚络合作用时域反射计介电松弛

In situ modifed screen printed and carbon paste ion selective electrodes for potentiometric determination of naphazoline hydrochloride in its formulation

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Journal of Pharmaceutical Analysis 2013年第5期3卷 367-375页

作者： Gehad G.mohamed f.A.Nour El-Dien Eman Y.Z.frag marwa El-Badry mohamed Chemistry Department Faculty of Science Cairo University

The construction and performance characteristics of new sensitive and selective in situ modified screen printed （ISPE） and carbon paste （ICPE） electrodes for determination of naphazoline hydrochloride （NPZ-HC1） have been developed. The electrodes under investigation show potentiometric response for NPZ-HC1 in the concentration range from 7.0 x 10-7 to 1.0 x 10-2 m at 25 ~C and the electrode response is independent of pH in the range of 3.1-7.9. These sensors have slope values of 59.7＋0.6 and 59.2＋0.2 mV decade-l with detection limit values of 5.6 ~ 10-7 and 5.9 x 10-7 m NPZ- HC1 using ISPE and ICPE, respectively. These electrodes show fast response time of 4-7 s and 5-8 s and exhibits lifetimes of 28 and 30 days for ISPE and ICPE, respectively. Selectivity for NPZ-HC1 with respect to a number of interfering materials was also investigated. It was found that there is no interference from the investigated inorganic cations, anions, sugars and other pharmaceutical excipients. The proposed sensors were applied for the determination of NPZ-HC1 in pharmaceutical formulation using the direct potentiometric method. It showed a mean average recovery of 100.2% and 102.6% for ISPE and ICPE, respectively. The obtained results using the proposed sensors were in good agreement with those obtained using the official method. The proposed sensors show significantly high selectivity, response time, accuracy, precision, limit of detection （LOD）and limit of quantification （LOQ） compared with other proposed methods.

关键词： ISPE and ICPE Potentiometry Naphazoline hydrochloride Eye drops

multimodal 4-arylchromene derivatives with microtubule-destabilizing,anti-angiogenic,and mYB-inhibitory activities

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Cancer Drug Resistance 2023年第1期6卷 59-77页

作者： Leonhard H.f.Kohler Sebastian Reich maria Yusenko Karl-Heinz Klempnauer Gerrit Begemann Rainer Schobert Bernhard Biersack Organic Chemistry Laboratory University of BayreuthBayreuth 95440Germany Institute for Biochemistry Westfalische-Wilhelms-UniversitatMunster 48149Germany Developmental Biology University of BayreuthBayreuth 95440Germany

Aim:Efficient and readily available anticancer drugs are sought as treatment *** this reason,chromene derivatives were prepared using the one-pot reaction and tested for their anticancer and anti-angiogenic ***:2-Amino-3-cyano-4-(aryl)-7-methoxy-4H-chromene compounds(2A-R)were repurposed or newly synthesized via a three-component reaction of 3-methoxyphenol,various aryl aldehydes,and *** performed assays to study the inhibition of tumor cell growth[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromid(mTT)assay],effects on microtubules(immunofluorescence),cell cycle(flow-activated cell sorting analysis),angiogenesis(zebrafish model),and mYB activity(luciferase reporter assay).fluorescence microscopy was applied for localization studies via copper-catalyzed azide-alkyne click reaction of an alkyne-tagged drug ***:Compounds 2A-C and 2f exhibited robust antiproliferative activities against several human cancer cell lines(50%inhibitory concentrations in the low nanomolar range)and showed potent mYB *** alkyne derivative 3 was localized in the cytoplasm after only 10 min of *** microtubule disruption and G2/m cell-cycle arrest were observed,where compound 2f stood out as a promising microtubule-disrupting *** study of anti-angiogenic properties showed that 2A was the only candidate with a high potential to inhibit blood vessel formation in ***:The close interplay of various mechanisms,including cell-cycle arrest,mYB inhibition,and anti-angiogenic activity,led to identifying promising multimodal anticancer drug candidates.

关键词： Chromene pyran anticancer drugs microtubule angiogenesis mYB inhibition

CTGf, intestinal stellate cells and carcinoid fi brogenesis

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World Journal of Gastroenterology 2007年第39期13卷 5208-5216页

作者： m Kidd Im modlin mD Shapiro RL Camp Sm mane W Usinger JR murren Departments of Surgery Yale University School of Medicine New Haven Connecticut 06520-8062 United States Departments of Pathology Yale University School of Medicine New Haven Connecticut 06520-8062 United States Departments of Affymetrix Resource Keck Biotechnology Resource Laboratory Yale University School of Medicine New Haven Connecticut 06520-8062 United States fibrogen Inc San Francisco CA United States Departments of medical Oncology Yale University School of Medicine New Haven Connecticut 06520-8062 United States

AIm： To investigate the role of small intestinal carcinoid tumor-derived fibrotic mediators, TGfβ1 and CTGf, in the mediation of fibrosis via activation of an ＂intestinal＂ stellate cell. mETHODS： GI carcinoid tumors were collected for Q RT-PCR analysis of CTGf and TGfβ1. markers of stellate cell desmoplasia were identified in peritoneal fibrosis by immunohistochemistry and stellate cells cultured from.f.esh resected fibrotic tissue. CTGf and TGfβ1 were evaluated using quantitative tissue array profiling （AQUA analysis） in a GI carcinoid tissue microarray （TmA） with immunostaining and correlated with clinical and histologically documented fibrosis. Serum CTGf was analyzed using a sandwich ELISA assay. RESULTS： message levels of both CTGf and TGfβ1 in SI carcinoid tumors were significantly increased （〉 2-fold, P 〈 0.05） versus normal mucosa and gastric （non-fibrotic） carcinoids. Activated stellate cells and markers of stellate cell-mediated fibrosis （vimentin, desmin） were identified in histological fibrosis. An intestinal stellate cell was immunocytochemically and biochemically characterized and its TGfβ1 （10-7m） initiated CTGf transcription response （〉 3-fold, P 〈 0.05） demonstrated. In SI carcinoid tumor patients with documented fibrosis, TmA analysis demonstrated higher CTGf immunostaining （AQUA Score： 92 ± 8, P 〈0.05）, as well as elevated TGfβ1 （90.6 ± 4.4, P 〈 0.05）. Plasma CTGf （normal 12.5 ± 2.6 ng/mL） was increased in SI carcinoid tumor patients （31 ± 10 ng/mL, P 〈 0.05） compared to non-fibrotic GI carcinoids （〈 15 ng/mL） CONCLUSION： SI carcinoid tumor fibrosis is a CTGf/ TGfβl-mediated stellate cell-driven fibrotic response. The delineation of the biology of fibrosis will facilitate diagnosis and enable development of agents to obviate its local and systemic complications.

关键词： Carcinoid Connective tissue growth factor fibrosis Small intestine Stellate cell TGfI

Extra-skeletal manifestations in mice affected by Clcn7-dependent autosomal dominant osteopetrosis type 2 clinical and therapeutic implications

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Bone Research 2019年第2期7卷 195-209页

作者： Antonio maurizi mattia Capulli Annabel Curle Rajvi Patel Argia Ucci Juliana Alves Cotes Harriet Oxford Shireen R. Lamandé John f. Bateman Nadia Rucci Anna Teti Department of Biotechnological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly murdoch Children’s Research Institute and University of melbourne MelbourneAustralia

Autosomal dominant osteopetrosis type 2 (ADO2) is a high-density brittle bone disease characterized by bone pain,multiple fractures and skeletal-related events,including nerve compression syndrome and hematological *** demonstrated that in mice carrying the heterozygous Clcn7^G213R mutation,whose human mutant homolog CLCN7^G215R affects patients,the clinical impacts of ADO2 extend beyond the skeleton,affecting several other *** hallmark of the extra-skeletal alterations is a consistent perivascular fibrosis,associated with high numbers of macrophages and lymphoid *** clinical information in a small cohort of patients confirms extra-skeletal alterations consistent with a systemic disease,in line with the observation that the CLCN7 gene is expressed in many ***2 mice also show anxiety and depression and their brains exhibit not only perivascular fibrosis but also β-amyloid accumulation and astrogliosis,suggesting the involvement of the nervous system in the pathogenesis of the ADO2 extra-skeletal ***-skeletal organs share a similar cellular pathology,confirmed also in vitro in bone marrow mononuclear cells and osteoclasts,characterized by an impairment of the exit pathway of the Clcn7 protein product,ClC7,through the Golgi,with consequent reduced ClC7 expression in late endosomes and lysosomes,associated with high vesicular pH and accumulation of autophagosome ***,an experimental siRNA therapy,previously proven to counteract the bone phenotype,also improves the extra-skeletal *** results could have important clinical implications,supporting the notion that a systematic evaluation of ADO2 patients for extra-skeletal symptoms could help improve their diagnosis,clinical management,and therapeutic options.

关键词： Extra-skeletal manifestations dominant osteopetrosis implications

Petrography and geochemistry of exported Colombian coals:Implications from correlation and regression analyses

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Energy Geoscience 2021年第3期2卷 201-210页

作者： Segun A.Akinyemi ferney Bohorquez Nazrul Islam Binoy K.Saikia Carlos H.Sampaio Tito J.Crissien Luis f.O.Silva Environmental Remediation&Geopollution Group Department of GeologyFaculty of ScienceEkiti State University Ado EkitiP.M.B.5363Ado EkitiNigeria Department of Civil and Environmental Engineering Universidad de La CostaCalle 58#55-66.080002BarranquillaAtlanticoColombia Coal and Energy Group Materials Science&Technology DivisionCSIR-North East Institute of Science&TechnologyJorhat785006India Departament D’Enginyeriaminera Industrial I TICSerra Húnter ProfUniversitatPolitecnica de Catalunya Barcelona TechAv.Bases de Manresa 61e63Manresa08242BarcelonaSpain

The petrology of coal,as determined by the microscopic analysis of organic and inorganic elemental constituents of coal,provides information on its nature and *** is used worldwide in the production of thermal energy and *** the case of high-quality Colombian coals,only limited studies have been carried *** present study presents the geochemical,mineralogical,and petrological characteristics of coal samples collected from Puerto Drummond in Cienaga,Colombia,to predict their potential ***,the ultimate,proximate,petrographic,gross calorific value(GCV),ash fusion temperature,fourier transform infrared spectroscopy(fTIR),X-ray diffraction(XRD),X-ray fluorescence(XRf),and Thermogravimetric(TG)analyses were employed in this *** petrological analysis reveals that Colombian coals are naturally more abundant in vitrinite(72%)than inertinite(14e23%)*** and aluminosilicate are the main minerals present as fine particles mixed with *** XRD and fTIR analyses show that the most common and dominant minerals are quartz,while gypsum,hematite,calcite and mica occur in lesser *** oxide composition of the coal ashes consists of 51e58%SiO2 and 18e25%Al2O3 as determined by XRf *** correlation and regression analysis,the moisture content shows a reverse correlation with GCV(Regression value of R2¼0.68).This study helps researchers to comprehend the importance of Colombian coals and presents various techniques for characterisation of coals.

关键词： Coal characterisation Geochemistry mineralogy Coal petrology Colombia