高效液相色谱法测定吲哚美辛控释胶囊的血药浓度和生物利用度

采用ＯＤＳ柱,甲醇－稀磷酸溶液（７６２４）为流动相,２６０ｎｍ为检测波长,建立了测定血浆中吲哚美辛浓度的高效液相色谱法,并测定了吲哚美辛控释胶囊炎痛康的血药浓度。结果表明,血浆中吲哚美辛浓度在０．１２５～５．０ｍｇ／Ｌ范围内线性关系良好（ｒ＝０．９９９６）,检测限６２．５μｇ／Ｌ（Ｓ／Ｎ＝３１）,平均回收率为１００．４％,日内和日间ＲＳＤ均小于５％。１１位受试者单剂量口服炎痛康后的相对生物利用度为１０２．３８％。     

吲哚美辛的毛细管电泳测定法研究

建立了制剂和体液中吲哚美辛的毛细管电泳高频电导分析法,并用于吲哚美辛肠溶片、复方吲哚美辛酊及血清、尿液中吲哚美辛含量的测定。对电泳介质的种类、浓度以及操作电压和进样量等影响因素进行了优化。实验采用3.0mmol／L乳酸＋0．68mol／L乙醇为电泳介质,分离电压为20.0kV,可在10min内实现对吲哚美辛的分离检测。在最佳实验条件下,吲哚美辛的线性范围为0.05μg／mL—100μg／mL,检出限为0．01μg／mL,回收率92.0％-105．1％。     

高效液相色谱-化学发光法测定复方吲哚美辛酊及人体尿液中的吲哚美辛

在酸性条件下,硫酸铈将分别氧化钌(II)联吡啶和吲哚美辛,产生的氧化产物会相互反应而发生化学发光。据此建立通过HPLC分离、用化学发光检测器测定吲哚美辛的方法。在优化的实验条件下,测定吲哚美辛的线性范围为22.95~61.20μg/mL,检出限(3σ)为6.12μg/mL,相对标准偏差为2.7%(n=11)。方法可用于生物药品复方吲哚美辛酊及人体尿液中吲哚美辛的含量。     

基于钨酸镍与氧化锌复合材料的电化学传感平台检测吲哚美辛EI北大核心CSCD

采用一锅法制备了钨酸镍与氧化锌复合材料(NiWO_(4)-ZnO),并对其进行了形貌表征、元素分析及比表面积测试,构筑了一种吲哚美辛电化学传感器。研究发现,NiWO_(4)-ZnO复合材料修饰玻碳电极对吲哚美辛表现出较高的检测灵敏度,在最优的实验条件下,吲哚美辛浓度与氧化峰电流成正比,在250~1082 pmol/L范围内呈现良好的线性关系,线性相关系数为0.9970,检出限为66.6 pmol/L。吲哚美辛电化学传感器应用于实际样品中吲哚美辛的测定,回收率为95.1%~98.3%,相对标准偏差为2.3%~3.8%,该传感器可用于药物分析领域。     

水溶液微悬浮聚合法制备酸性药物吲哚美辛分子印迹微球及其色谱表征

以带有羧基的酸性药物吲哚美辛为模板分子、碱性的4-乙烯基吡啶为功能单体,采用水溶液微悬浮聚合法制备了用于色谱分离的微米级分子印迹微球.详细讨论了流动相中缓冲溶液的pH值对吲哚美辛在MIMs柱上的容量因子(k′)、分离因子(α)和印迹因子(β)的影响.通过MIMs柱对吲哚美辛和4-氨基吡啶(4-AP)的保留行为的比较,证明以4-乙烯基吡啶为功能单体制得的MIMs对吲哚美辛的识别作用,主要靠吡啶环上氮原子与吲哚美辛羧基之间的离子键相互作用,以及吡啶环与模板分子之间的π-π相互作用.     

吲哚美辛在单壁碳纳米管修饰电极上的电化学行为

运用伏安法研究了吲哚美辛在单壁碳纳米管修饰电极上的电化学行为.在0.1 mol/L HAc-NaAc缓冲溶液(pH 4.5)中,吲哚美辛于0.91 V (vs.SCE)电位处有一个峰形很好的氧化峰.与裸玻碳电极相比,吲哚美辛在修饰电极上的电位正移了约30 mV,峰电流增加了近10倍,表明该修饰电极对吲哚美辛有较强的电催化作用.搅拌条件下开路富集2 min,氧化峰电流与吲哚美辛在5.5×10-7～1.1×10-5 mol/L浓度范围内呈良好的线性关系,检出限为1.1×10-7 mol/L.该方法可用于药剂中吲哚美辛的分析.     

酶联免疫吸附分析法测定环境水样中痕量药物吲哚美辛

将吲哚美辛与蛋白质载体结合,制成完全免疫抗原,经过多次动物免疫得到了性能优良的兔抗吲哚美辛抗体,在优化实验条件的基础上,建立了灵敏度高、特异性强、简便、稳定的测定水样中吲哚美辛的酶联免疫吸附分析方法(ELISA).IC50值(标准曲线中吸光度抑制至最大吸光度值的50%时所对应的待测物浓度)为0.09μg/L～0.17 μg/L,最低检出限为 0.005μg/L～0.01 μg/L.真实水样中,均发现含有吲哚美辛,浓度在0.016 μg/L~0.083 μg/L之间,水样的加标回收率在84.4%～127.0%之间.     

N-苯磺酰基-3-乙酰基吲哚羰基酰腙类衍生物合成及其体外抗HIV-1活性研究（英文）

基于长期进行的抗HIV-1抑制剂研究,通过优化路线并设计合成了26个N-苯磺酰基-3-乙酰基吲哚羰基酰腙类衍生物(3a～3z)。该方法环保,为今后制备腙类化合物提供了绿色合成途径。所有目标化合物在体外均测定了其对HIV-1抑制活性。结果表明,化合物3a、3g、3t和3w～3y表现出较好的抗HIV-1活性,特别是N-苯磺酰基-3-乙酰基吲哚-3-甲基苯甲酰腙(3a)和N-(3-硝基)-苯磺酰基-3-乙酰基-6-甲基吲哚-2-噻吩甲酰腙(3t)表现出显著的抗HIV-1活性,其对应EC_(50)值分别为0.77和0.74μg/mL,TI值分别为259.74和270.27。因此,化合物3a和3t可作为候选化合物经进一步结构优化研究其HIV-1活性。     

无过渡金属催化条件下合成3,3'-二吲哚甲烷衍生物的最新进展（英文）

3,3'-二吲哚甲烷类化合物是一类重要的吲哚生物碱,其结构单元广泛存在于天然产物、功能性材料以及合成药物分子中.因其具有多样的生物活性和功能,如抗氧化、抗炎症、抗血管生成、抗菌以及抗癌活性等,构筑3,3'-二吲哚甲烷类杂环化合物备受关注.传统的合成方法,尤其是对称结构的3,3'-二吲哚甲烷类化合物的合成主要在化学量的Br?nsted酸或Lewis酸存在下,吲哚衍生物与羰基化合物经傅-克反应缩合得到.而过渡金属的使用可引起化合物中金属残留以及环境污染.总结和探讨了从2010年至今3,3'-二吲哚甲烷类化合物的合成方法,尤其是对无过渡金属参与条件下,对称结构的3,3'-二吲哚甲烷类化合物以及非对称结构3,3'-二吲哚甲烷类化合物制备的最新进展以及相应的反应机理,旨在为该类化合物生物活性测试提供重要的理论依据和技术支持.     

吲哚美辛纳米胶体金分子印迹聚合物的制备及其在固相萃取中的应用

以吲哚美辛(IDM)为模板分子,丙烯酰胺(AA)为功能单体,乙二醇二甲基丙烯酸酯(EGDMA)为交联剂,本体聚合法制备过程中加入纳米胶体金,合成了吲哚美辛胶体金分子印迹聚合物(MIPs/Au),利用MIPs/Au表面胶体金对蛋白吸附作用,将抗吲哚美辛的多克隆抗体固定在MIPs/Au上,得到表面固定有抗体的新型聚合物(MIPs/Au-Ab)并对其进行了表征。制备了填充材料为MIPs/Au-Ab的固相萃取柱并对其上样、淋洗和洗脱条件进行了优化,并将所制备的新型萃取柱用于水样中IDM的分离富集。抗吲哚美辛抗体交联在聚合物表面,不仅增加了萃取柱的特异性吸附容量,而且有效地降低了MIP的非特异性吸附。     

Cell Uptake and Trafficking Behavior of Non‐covalent,Coiled‐coil Based Polymer–Drug Conjugates

This paper reports on the cell uptake and trafficking properties of a series of non‐covalent polymer–drug conjugates. These nanomedicines are composed of a poly(N‐(2‐hydroxypropyl)methacrylamide) backbone functionalized with multiple copies of a drug. The drug moieties are attached to the polymer via a non‐covalent, so called coiled coil motif, which is formed by heterodimerization of two complementary peptide strands, one of which is attached to the polymer carrier and the other to the drug. Cytotoxicity and FACS experiments, which were carried out with model anticancer drug or fluorophore conjugates, provided insight into the cell uptake and trafficking behavior of these conjugates.

     

Synthesis of aryltrifluoromethylpyridazines application to the synthesis of rod‐like molecules as liquid crystals diazines part 46

Conjugated oligomers with a trifluoromethylpyridazine unit have been synthesized by Suzuki crosscoupling reaction. These oligomers could be used as building block for construction of supramolecules or as liquid crystals when they are substituted by long chain alkoxy groups.     

Monocyclic zwitterionic lambda(5)Si-silicates with an SiO(2)FC(2) framework: syntheses and structural characterization in the solid state and in solution

Treatment of the acyclic zwitterionic pentacoordinate silicate F(3)MeSiCH(2)NMe(2)H with 1 molar equiv of Me(3)SiOC(6)H(4)OSiMe(3), Me(3)SiOCH(2)C(O)OSiMe(3), Me(3)SiOC(Ph)=NOSiMe(3), or Me(3)SiOC(O)C(O)OSiMe(3) (solvent CH(3)CN, room temperature) yielded the respective monocyclic zwitterionic pentacoordinate silicates (11a), (12a), (13a), and (14a), along with 2 molar equiv of Me(3)SiF. The derivatives 11b-14b with a 2,2,6,6-tetramethylpiperidinio substituent instead of the dimethylammonio group were prepared analogously, starting from F(3)MeSiCH(2)NR(2)H (NR(2)H = 2,2,6,6-tetramethylpiperidinio). Single-crystal X-ray diffraction studies showed that the Si-coordination polyhedra of 11a.1.5CH(3)CN, 12a-14a, and 11b-14b are distorted trigonal bipyramids, the axial positions being occupied by the fluorine atom and one of the two oxygen atoms (12a/12b, carboxylate oxygen atom; 13a/13b, carbon-linked oxygen atom). These results are in agreement with the NMR data ((1)H, (13)C, (19)F, (29)Si) obtained for these compounds in solution. The chiral (C(1) symmetry) zwitterions 11a-14a and 11b-14b exist as pairs of (A)- and (C)-enantiomers in solution. VT (1)H NMR studies with 11b-14b in CH(3)CN in the temperature range 25-85 degrees C gave no indications for an enantiomerization process [(A)/(C)-enantiomerization] at the silicon atom.     

Controlled intracellular localization and enhanced antisense effect of oligonucleotides by chemical conjugation

Oligonucleotides can be covalently linked to peptides composed of any sequence of amino acids by solid phase fragment condensation. The peptides incorporated into the conjugates include nuclear localizing signals (NLS), nuclear export signals (NES), membrane fusion domain of some viral proteins and some designed peptides with amphipathic character. Evaluation of biological properties of DNA-peptide conjugates indicated that (a) the conjugates could bind to target RNA and dsDNA with increased affinity, (b) the conjugates were more resistant to cellular nuclease degradation, (c) the conjugate-RNA hybrids could activate RNase H as effectively as native oligonucleotides, (d) the conjugates with fusion peptides showed largely enhanced cellular uptake, (e) the conjugates with NLS could be predominantly delivered into the cell nucleus, (f) the conjugates with NES could be localized in the cytoplasm. As a result, antisense oligonucleotides conjugated with NLS could inhibit human telomerase in human leukemia cells much more strongly than phosphorothioate oligonucleotides.     

Synthesis of heterocyclic compounds using amidines as their ene‐1,1‐diamine tautomers. II. Synthesis of 2,3‐dihydropyridine, 3,4‐dihydropyridine and 3,4‐dihydropyrrol‐2‐one derivatives by the reaction of amidines with α, β‐unsaturated carbonyl compounds

N‐t‐Butylacetamidines 1 on heating with methyl vinyl ketone, acrolein or crotonaldehyde gave the 2,3‐dihydropyridine derivatives 4,5 or 6 via N‐alkylation of the acetamidines 1 . Reaction of amidines 1 with phenyl 1‐propenyl ketone, benzalacetone or chalcone gave 3,4‐dihydropyridine derivatives 8, 9 or 10 . These were obtained by C‐alkylation, achieved by Michael addition of the acetamidines 1 as their N,C‐tautomers ene‐1,1‐diamines 1 ′ to α,β‐unsaturated carbonyl compounds, and subsequent cyclodehydration of adducts. Reaction of 1 with ethyl 3‐benzoylacrylate gave 3,4‐dihydropyrrol‐2‐one derivatives 13 .     

The Design of Polymer‐based Nanocarriers for Effective Transdermal Delivery

This study reports a facile and practical means to non‐invasively deliver biologically active ingredients through the skin using polymer‐based nanocarriers. For this, polymer nanocapsules were fabricated with different surface charges as well as glass transition temperatures and we observed their ability to deliver the encapsulated active ingredient, coenzyme Q10, through the skin layer. Direct imaging of a probe molecule, Nile Red, and a matrix polymer labeled with fluorescence moiety, Lucifer Yellow, allowed us to demonstrate that the probe molecule readily permeates into the deep skin, while the matrix polymer stays in the stratum corneum layer due to electrostatic interactions. Quantitative characterization of the penetrating amount of coenzyme Q10 using the Frantz cell method proved that, to achieve improved delivery efficiency, the nanocapsule should have a low glass transition temperature as well as positive surface charges.

     

An efficient preparation of new homoallylamines and α‐aminonitriles bearing furyl and thienyl rings

New diverse N‐aryl‐N‐[1‐furyl(thienyl)but‐3‐enyl]amines (homoallylamines) or 2‐(N‐arylmethylamino)‐2‐furyl(thienyl)acetonitriles (α‐aminonitriles) were easily prepared in good to excellent yields by an indium‐mediated Barbier‐type reaction between N‐hetarylaldimines and allyl bromide in MeOH or a direct three component reaction between anilines, hetaryl aldehydes and trimethylsilyl cyanide in the presence of a catalytic amount of molecular iodine at room temperature, respectively. The entire set of amines was characterized by IR, ¹H and ¹³C NMR spectroscopy.     

Synthesis of Indomethacin Conjugates with D-Glucosamine

Two series of indomethacin conjugates with D-glucosamine were prepared with the objectives of reducing ulcerogenic potency, increasing the bioavailability of indomethacin and exerting the coordinative effects on osteoarthritis. The structures of the conjugates were identified by ^1H NMR and ^13C NMR. The ester conjugates inhibited edema as potent as indomethacin.     

Synthesis and Biological Activities of Diosgenin-Triazole Conjugates with a 1,3-Dipolar Cycloaddition Reaction

Chemistry of Natural Compounds - A novel series of diosgenin-triazole conjugates (10a–d, 11a–c, 12a–c, 13a–c) was designed and synthesized as antifungal agents by using a...     

Synthesis Of 1,8‐dioxa‐dibenzo[e,h]azulenese

A novel synthetic route to 2‐methyl‐1,8‐dioxa‐dibenzo[e,h]azulenes [1] via cyclisation of the corresponding 1,4‐dicarbonyl compound is described. 1,4‐Dicarbonyl compounds were synthesized by the alkylation reaction of the 11H‐dibenzo[b,f]oxepine‐10‐one while analogous alkylation of 11H‐dibenzo[b,f]thiepine‐10‐one resulted in formation of O‐alkylated products. Selective oxidation of 2‐methyl group afforded 1,8‐dioxa‐dibenzo[e,h]azulenes with formyl and hydroxymethyl functionality at C(2) position.