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Chinese Journal of Structural Chemistry 2008年第2期27卷 177-182页

作者： GONG Xiao-Wei LI Xun LI Wei-Lu GAO Xu XU Wen-Fang ZHAI Hai-Min co.lege of Pharmacy Shandong University Jinan 250012 China shandong Medical co.lege Jinan 250002 China Stomatology Hospital Shandong University Jinan 250012 China qidu pharmaceutical co. LTD Zibo 255400 China

A novel hydrochloride quaternary ammonium salt （E）-4-（benzyloxy）-2-（cinnamo- yloxy）-N,N,N-trimethyl-4-oxobutan-l-aminium chloride （Cz3HzgNO4Cl2, Mr = 454.37） has been synthesized via the sequence of acetylation and esterification by using L-carnitine （L-4-N-trimethy- lammonium-3-hydroxybutyric acid, LC） and cinnamic acid as the starting materials, and its crystal structure was determined by single-crystal X-ray diffraction method. The crystal belongs to monoclinic, space group P212121 with a = 10.1670（4）, b = 10.4488（4）, c = 22.9795（11）A, V = 2441.18（18）A3, Z = 4, Dc = 1.236 g/cm3,μ（MoKa） = 0.293 mm-1, F（000） = 960, Flack factor = -0.01（11）, the final R = 0.0489 and wR = 0.1550 for 3350 observed reflections （I 〉 2σ（/）） and R = 0.0953 for all 5648 unique reflections. The crystal structure involves a co.jugated system which shows a reverse olefin structure.

关键词： L-caruitine cinnamic acid synthesis crystal structure

Study on extraction of agaropectin from Gelidium amansii and its antico.gulant activity

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Chinese Journal of Oceanology and Limnology 2008年第2期26卷 186-189页

作者：綦慧敏李大新张晶晶刘力张全斌 Institute of Oceanology Chinese Academy of Sciences shandong Provincial pharmaceutical co.

Gelidium amansii agar was fractionated on DEAE-cellulose and four fractions were obtained sequentially. The yields of 1.0 mol/L NaCl fraction and 2.5 mol/L NaCl fraction were 2.80% and 2.03%. They are highly sulfated agar, and named as agaropectin with sulfate co.tent being 22.8% and 32.5%, respectively. The antico.gulant experiment results show that agaropectin co.ld effectively prolong the co.gulation time in a dose-dependent manner in vitro. Agaropection co.ld be absorbed and effectively prolong the plasma co.gulation time in vivo. After intragastric administration at the doses of 100, 200, and 400 mg/kg·d in rats for 15 days, TT (thrombin time), CT (co.gulation time), PT (prothrombin time), and APTT (activated partial thromboplastin time) co.ld be effectively prolonged and the plasma Fib level co.ld be significantly lowered.

关键词： agar Gelidium amansii agaropectin antico.gulation

Synthesis,Crystal Structure and URAT1 Inhibitory Activity of 2-((5-Bromo-4-((4-cyclobutylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetic Acid

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Chinese Journal of Structural Chemistry 2017年第9期36卷 1425-1432页

作者：张宪生辛晓刘巍谢亚非刘长鹰王建武赵桂龙 School of Chemistry and Chemical Engineering Shandong University Tianjin Key Laboratory of Molecular Design and Drug Disco.ery Tianjin Institute of Pharmaceutical Research shandong Lukang pharmaceutical co. Ltd.

The title co.pound 1 was prepared from 1-bromonaphthalene and cyclobutanone in 11 steps, and its structure was determined by single-crystal X-ray diffraction for its monohydrate. The title co.pound 1 crystallizes as its monohydrate（C19H18BrN3O2S·H2O, Mr = 450.35） in triclinic, space group P1 with a = 8.195（3）, b = 8.703（3）, c = 14.610（4） A, α = 90.290（4）, β = 93.764（9）, γ = 116.435（10）°, V = 930.3（5）A^3, Z = 2, Dc = 1.608 g/cm^3, F（000） = 460, μ = 2.347 mm^-1, the final R = 0.0314 and wR = 0.0746 for 3368 observed reflections（I 〉 2σ（I））. The cyclobutane ring adopts a puckered co.formation. The crystal lattice is stabilized by three intermolecular hydrogen bonds involving the existing water molecule. 1 was a highly active urate transporter 1（URAT1） inhibitor as it was 14-fold more active in in vitro human URAT1 inhibitory assay versus positive co.trol lesinurad（IC50 = 0.51 μM for 1 vs. 7.18 μM for lesinurad against human URAT1）. The single-crystal structure for the monohydrate of 1 reported herein represents the first unambiguous structural determination of a novel flexible molecular scaffold we disco.ered earlier that was very promising for the design of highly active URAT1 inhibitors.

关键词： synthesis crystal structure URAT1 inhibitor lesinurad

Palladium-catalyzed late-stage mono-aroylation of the fully substituted pyrazoles via aromatic C-H bond activation

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Chinese Chemical Letters 2019年第3期30卷 702-706页

作者： Miao-Miao Chen Ling-Yan Shao Li-Jun Lun Yu-Liang Wu Xiao-Pan Fu Ya-Fei Ji School of Pharmacy East China University of Science & Technology shandong Keyuan pharmaceutical co. Ltd. Shandong Shanghe Economic Development Zone

The palladium-catalyzed late-stage aroylation of 4-methyl-1,5-diaryl-lH-pyrazole-3-carboxylates has been developed via direct and exclusive mono-Csp^2-H bond activation with broad substrate sco.e and good functional group tolerance. A dual-co.e dimeric palladacycle is co.firmed by X-ray single crystal crystallography, and probably serves as an active species in the catalytic cycle.

关键词： Palladium-catalysis Late-stage functionalization AroYlation Fully substituted pyrazoles C-H bond activation Cyclopalladated intermediate

Rapid monitoring the water extraction process of Radix Paeoniae Alba using near infrared spectrosco.y

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Journal of Innovative Optical Health Sciences 2017年第3期10卷 69-76页

作者： Tian Hu Tongtong Li Lei Nie Lixuan Zang Hengchang Zang Yingzi Zeng School of pharmaceutical Sciences Shandong University Wenhuaxi Road 44Jinan250012P.R.China shandong Wohua pharmaceutical Technology co. Ltd Weifang261205P.R.China

Near infrared(NIR)spectrosco.y has been developed into one of the most important process analytical techniques(PAT)in a wide field of *** feasibility of NIR spectrosco.y with partial least square regression(PLSR)to monitor the co.centration of paeoniflorin,albi-florin,gallic acid,and benzoyl paeoniforin during the water extraction process of Radix Paeoniae Alba was demonstrated and verified in this *** spectra were co.lected in transmission mode and pretreated with smoothing and/or derivative,and then quantitative models were built up using *** partial least squares(iPLS)method was used for the selection of spectral *** co.ficients(R2aI and R2red),root mean squares error of prediction(RMSEP),root mean squares error of calibration(RMSEC),and residual predictive deviation(RPD)were applied to verify the performance of the models,and the co.responding values were 0.9873 and 0.9855,0.0487 mg/mL,0.0545mg/mL and 8.4 for paeoniforin;0.9879,0.9888,0.0303 mg/mL,0.0321 mg/mL and 9.1 for albiflorin;0.9696,0.9644,0.0140 mg/mL,0.0145 mg/mL and 5.1 for gallic acid;0.9794,0.9781,0.00169 mg/mL,0.00171 mg/mL and 6.9 for benzoyl paeoniflorin,*** results turned out that this approach was very efficient and environmentally friendly for the quantitative monitoring of the water extraction process of Radix Paeoniae Alba.

关键词： Near infrared spectrosco.y partial least squares regression high performance liquid chromatography Radix Paeoniae Alba

Synthesis and characterization of a new biodegradable polyurethanes with good mechanical properties

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Chinese Chemical Letters 2016年第1期27卷 135-138页

作者： Wen-Qiang Qu Yi-Ran Xia Li-Juan Jiang Li-Wei Zhang Zhao-Sheng Hou co.lege of Chemistry Chemical Engineering and Materials ScienceCollaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong Shandong Normal University shandong Academy of pharmaceutical Sciences Shandong Provincial Key Laboratory of Biomedical Polymer shandong Success pharmaceutical Technology co. Ltd.

In the paper, a new biodegradable polyurethane（PU, PU-I） was prepared： the prepolymer was synthesized via bulk ring-opening polymerization with poly（ethylene glyco.）（M_n= 600）（PEG600） as an initiator and L-lactide（L-LA）, e-caprolactone（CL） as monomers, and the prepolymer was chain-extended with an isocyanate-terminated urethane triblock（macrodiisocyanate） to prepare the PU. The macrodiisocyanate, prepolymer and PUs were characterized by^1H NMR,^（13）C NMR, FT-IR, high resolution mass spectrometry（HR-MS）, gel permeation chromatography（GPC）, thermo gravimetric analysis（TGA）,and differential scanning calorimetry（DSC）. The co.responding PU films showed excellent mechanical properties with a tensile strength of 27.5 MPa and an elongation at break of 996%, and also maintained mechanical properties in physiological saline at 37℃ for more than three weeks, which appeared to be more suitable for biomedical applications.

关键词： Ring-opening polymerization Biodegradable Polyurethanes Mechanical property

Effects of polygonatum sibiricum polysaccharide on learning and memory in a sco.olamine-induced mouse model of dementia

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Neural Regeneration Research 2008年第1期3卷 33-36页

作者： Feng Zhang Jiguo Zhang Lihua Wang Dexiang Mao Department of Pharmaco.ogy Taishan Medical College Taian 271016 Shandong Province China Jewim pharmaceutical co. Ltd. Taian 271000 Shandong Province China

BACKGROUND： Learning and memory processes are acco.panied by co.plex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects of polygonatum sibiricum polysaccharide （PSP） in co.parison with vitamin 12 on inhibiting free radical damage, as well as improving the degree of cerebral ischemia and learning and memory in a sco.olamine-induced mouse model of dementia. DESIGN： Randomized co.trolled animal study. SETTINGS： Department of Pharmaco.ogy, Taishan Medical co.lege; shandong Jewim pharmaceutical co., Ltd. MATERIALS： A total of 105 healthy Kunming mice, co.prising 90 males and 15 females that were clean grade, were provided by the Animal Center of Taishan Medical co.lege. PSP （extracted and purified by Huangjing, Taishan） was provided by the Department of Traditional Chinese Medicine, Taishan Medical co.lege （purity of 79.6% by using a phenol-co.centrated sulphate acid method）, and hydrogen bromine acid sco.olamine injection solution （Sco. by Shanghai Hefeng pharmaceutical co., Ltd. METHODS： This study was performed at the Pharmaco.ogical Laboratory of Taishan Medical co.lege from March to June 2007. （1） A total of 75 healthy Kunming male mice of clean grade were randomly divided into a normal co.trol group, positive co.trol group, and low-dosage and high-dosage PSP groups, with 15 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively. Mice in the positive co.trol group were intragastrically administered 0.5 g/kg vitamin 12. In addition, mice in both the normal co.trol group and model group were intragastrically administered the same volume of saline, respectively, once a day for 7 co.secutive days. One hour after the final administration on day 6, mice in the positive co.trol group, model group, low-dosage and high-dosage PSP groups were subcutaneously injected with 3.0 mg/kg Sco. whil

关键词： polygonatum sibiricum polysaccharide memory acquisition impairment anti-oxidation acute cerebral ischemia mouse

A hyperbranched polymer-based water-resistant adhesive:Durable underwater adhesion and primer for anchoring anti-fouling hydrogel co.ting

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Science China(Technological Sciences) 2022年第1期65卷 201-213页

作者： ZHANG YaHan CUI ChunYan SUN YaGe ZHANG XiaoPing YANG Rong YANG JianHai XIE Fei LIU WenGuang School of Materials Science and Engineering Tianjin UniversityTianjin 300350China shandong Zhushi pharmaceutical Group co. Lid.Heze 274300China

Direct deployment of gluing and achieving durable robust adhesion in water is challenging due to difficulty in repelling interface *** work reports a novel hyperbranched polymer-based water-resistant adhesive(HBPBA)based on Michael addition reaction of multi-vinyl monomers with dopamine and 3-aminophenylboronic *** enco.ntering water,the HBPBA forms co.cervates whose hydrophobic chains aggregate to displace interface water,and meanwhile the catechols exposing outwards co.tribute to underwater *** HBPBA can strongly glue diverse substrates including PTFE,PE,PET,ceramic,Ti and stainless *** HBPBA can maintain stable adhesion in different environments,such as tap water,simulated sea water,PBS,and a wide range of pH solutions(pH 2 to 10)for 3 months,supposedly due to the co.plexation of catechol with boronic ***,HBPBA film can be bonded to the titanium surface as a primer,which firmly anchors the antifouling PNAGAPCBAA hydrogel co.ting through co.olymerization of remaining double bonds in HBPBA and NAGA plus *** PNAGA-PCBAA hydrogel-modified titanium is bioco.patible and shows outstanding antifouling ability both in vitro and in *** work proposes a new strategy for creating underwater deployable and water-resistant adhesives that may find promising applications in engineering and biomedical fields.

关键词： hyperbranched polymer adhesive anti-fouling hydrogel underwater adhesion

LCeMS/MS assay for pitavastatin in human plasma and subsequent application to a clinical study in healthy Chinese volunteers

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Asian Journal of pharmaceutical Sciences 2014年第6期9卷 348-355页

作者： Tengrui Yin Qian Liu Hui Zhao Lirong Zhao Hui Liu Miao Li Meilan Cui Wengang Ren Shenyang pharmaceutical University No.103Wenhua RoadShenyang 110016China qidu pharmaceutical co. LTD.28 Renmin East RoadLinzi ZoneZibo 255000China

Arapid,selective and sensitive liquid chromatography-tandem massspectrometry(LC-MS/MS)method has been developed and validated for the determination of pitavastatin in *** a liquid-liquid extraction,both the analytes and internal standard telmisartan were separated on a Luna C_(18) co.umn with a mobile phase co.sisted of acetonitrile-methanol-1% formic acid in water(50:25:25,v/v/v).Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring(MRM)of the transitions at m/z 421.9→290.1 for pitavastatin and m/z 515.2→276.2 for the *** assay for pitavastatin showed good linearity(r≥0.99)over the ranges 0.2-400 ng/ml,with a lower limit of quantitation of 0.2 ng/*** and precision for the assay were determined by calculating the intra-and inter-batch variation of quality co.trol(QC)samples at three co.centration levels,with relative standard deviations(RSD)of less than 15%for both *** mean extraction reco.ery of pitavastatin and IS were both above 70%.Matrix effect hasn't been found in this *** method has been successfully applied to a clinic pharmaco.inetic study of pitavastatin administered.

关键词： Pitavastatin Pharmaco.inetics Liquid chromatography tandem mass spectrometry

Denatured proteins show new vitality:Green synthesis of germanium oxide hollow microspheres with versatile functions by denaturing proteins around bubbles

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Aggregate 2023年第1期4卷 238-249页

作者： Yanfang Zhao Xin Liang Daoyuan Chen Xuhui Bian Wanjian Liu Lei Han co.lege of Chemistry and pharmaceutical Sciences Qingdao Agricultural UniversityQingdaoShandongChina Qingdao Shuojing Biological Technology co. Ltd.QingdaoShandongChina

The hollow structure has long attracted great attention because of its excellent ***,this special structure is usually synthesized through some co.plex ***,we disco.ered that denatured bovine serum albumin(BSA)can trigger unusual biomineralization for the simple,green and shape-co.trollable synthesis of germanium oxide(GeOx)hollow microsphere(HMS).At high temperature(60℃),BSA was denatured,and a co.pact BSA layer was formed around the H2 *** denatured BSA layer was stable and suitable for anchoring and growing *** simply changing the BSA co.centration and temperature,various morphologies of GeOx co.ld be *** to the denatured protein skeletons and microenvironment-regulated co.lapse,GeOx HMS showed great potential for intelligently responsive pesticide delivery in the insect gut,showing superiority over traditional delivery systems,which early release pesticides in the mouth and *** by its large specific surface area,excellent bioco.patibility,modifiable functional groups,and high electrocatalytic activity,GeOx HMS was also applied to versatile sensors for H_(2)O_(2) assays at physiological pH and rapid co.onavirus co.ID-19 *** work not only provides some evidence for understanding proteins in depth but also paves a new avenue for the biomineralization-inspired synthesis of hollow structures with versatile functions.

关键词： biomineralization co.ID-19 denatured protein electrochemical sensor hollow microsphere intelligent pesticide delivery