金雀异黄素4′-二氟甲醚化衍生物的合成

目的 合成金雀异黄素4′-二氟甲醚化衍生物。方法 金雀异黄素与HCF2Cl、NaOH在水和二氧六环的混合液中发生二氟甲醚化反应，生成7，4′-二-二氟甲氧基-5-羟基异黄酮（2）、7-二氟甲氧基-5，4′_二羟基异黄酮（3）和4′-二氟甲氧基-5，7-二羟基异黄酮（4），再经甲醚化反应得到7-二氟甲氧基-5，4′-二甲氧基异黄酮（5）和4′-二氟甲氧基-5，7-二甲氧基异黄酮（6）。结果 化合物的结构经MS、^1H-NMR、^13C-NMR、^19F-NMR等进行了确证，化合物（4）和（6）为首次合成的新化舍物。结论 为金雀异黄素4′-二氟甲醚化衍生物的合成提供了实验基础。     

莫西沙星8-二氟甲氧基类似物的合成与体内外抗菌作用

1-环丙基-6，7-二氟-8-甲氧基-1，4-二氢．4-氧代喹啉．3-羧酸乙酯依次经醚键断裂、酯化、二氟甲基醚化得1．环丙基-6，7-二氟-8-二氟甲氧基-1，4-二氢-4-氧代喹啉．3-羧酸乙酯，然后经过螫合、与[1S，6S]-2．叔丁氧羰基．2，8．二氮杂双环[4，3，0]壬烷缩合、最后脱除叔丁氧羰基保护得到1-环丙基．8．二氟甲氧基-7-[（1S，6S）．2，8．二氮杂双环[4，3，0]壬烷．8．基]-6-氟．1，4-二氢-4-氧代喹啉-3-羧酸。目标化合物的结构经核磁共振氢谱和质谱（ESI）所确证，并测定了其体内外抗菌作用，结果表明该化合物优于对照药环丙沙星，与莫西沙星相当或略优，尤其对肺炎链球菌29074的体内活性突出，值得深入评价。     

中国南海软珊瑚 Dendronephthya gigantea 中的多羟基甾醇成分

从中国南海三亚海域采集的软珊瑚Dendronephthya gigantea中，分离得到6个甾醇类成分，分别为胆甾醇(I)，胆甾-5-烯-3β，7β二醇(Ⅱ)，胆甾-5，22(E)-二烯-3β，7α-二醇(Ⅲ)，24-亚甲基-胆甾-5-烯-3β，7α-二醇(Ⅳ)，24-甲基-胆甾-5，22(E)-二烯-3β，7α-二醇(V)和胆甾-5-烯-3β,7α二醇(Ⅵ)。应用^1H,^13C NMR,EIMS等谱学方法确定了它们的结构。化合物Ⅰ～Ⅵ均为首次从该种属软珊瑚中分离得到。     

3,5-二叔丁基-4-羟基苯甲酸的合成

以2，6-二叔丁基-4-甲基苯酚为原料，在乙酸溶液中与溴反应形成3，5-二叔丁基-4-羟基苯甲醛，然后经Jones氧化得到3，5-二叔丁基-4-羟基苯甲酸，总收率63．7％。     

1，4-二氢-2,6-二甲基-4-（3-硝基苯基）-3,5-吡啶-1羧酸单甲酯的制备

1，4-二氢-2,6-二甲基-4-（3-硝基苯基）-3,5-吡啶二羧酸单甲酯（1）是二氢吡啶类降压药的重要中间体。主要合成方法如下：（1）1,4．二氢-2,6-二甲基-4-（3-硝基苯基）-3，5-吡啶二羧酸甲基氰乙基酯经碱性水解制得，收率60％，但原料不易得；（2）1-乙氧甲基-1，4-二氢-2,6-二甲基-4-（3-硝基苯基）-3，5-吡啶羧酸二甲酯在金属钠和二甲胺基异丙醇存在下水解、酸化制得，收率47．4％，操作繁琐，后处理困难；     

烯烃高收率制备手性邻二醇新方法

烯烃在催化剂锇酸盐交换的氯磷灰石（CAP—OSO4有制法）和手性配体双（二氢奎宁-9）-2，3-二氮杂萘-1，4-二醚[（DHQ）2PHAL]或双（二氢奎尼丁-9）-2，3-二氮杂萘-1，4-二醚[（DHQD）2PHAL]作用下高选择性制备相应的手性邻二醇。8例收率71％～96％，ee值90％～97％。催化剂回收方便，循环利用5次，收率和ee值稳定。     

醋酸孕双烯醇酮中微量杂质的分离和结构确证

从醋酸孕双烯醇酮中分得4个微量杂质，经IR、NMR和MS确证它们的结构分别为：3β-乙酰氧基-孕甾-5，16-二烯-7，20-二酮、3β-乙酰氧基-雄甾-5，16-二烯-17-羧酸、3β-乙酰氧基-16β-羟基-孕甾-5-烯-20-羧酸-γ-内酯和孕甾-4，6，16-三烯-3，20-二酮。     

盐酸吉西他滨的合成

2-脱氧-2，2-二氟-D-赤型-呋喃戊糖-1-酮-3，5-二苯甲酸酯经四氢锂铝还原、甲磺酰化得2-脱氧-2，2-二氟-D-呋喃核糖-3，5-二苯甲酸酯-1-甲磺酸酯，与胞嘧啶缩合后在含氨甲醇中脱保护基，成盐后于含水丙酮中结晶分离得盐酸吉西他滨，总收率14％。     

浅裂鳞毛蕨中的一个新二氢黄酮

目的研究浅裂鳞毛蕨(Dryopteris sublaeta Ching et Hsu)的化学成分。方法利用硅胶柱色谱进行分离纯化，根据化合物的理化性质和光谱数据鉴定结构。结果从浅裂鳞毛蕨中分离并鉴定了4个化合物，分别为：2(S)-5,7,3′-三羟基-6,8-二甲基-5′-甲氧基-二氢黄酮(1)，荚果蕨素(5,7-二羟基-6,8-二甲基-4′-甲氧基-二氢黄酮，matteucinol)(2)，去甲氧基荚果蕨素(5,7-二羟基-6,8-二甲基-二氢黄酮，desmethoxymatteucinol)(3)和2′-羟基去甲氧基荚果蕨素(5,7,2′-三羟基-6,8-二甲基-二氢黄酮,2′-hydroxy-desmethoxymatteucinol)(4)。结论化合物1为新化合物，其余化合物均为首次从该属植物中分离得到。     

普卢利沙星关键中间体的合成

3，4-二氟苯胺经一系列反应制得[（3，4-二氟苯胺基）（乙硫基）亚甲基]丙二酸二乙酯，再经闭环、羟基保护、氯代，最后脱保护、闭环得到普卢利沙星关键中间体6，7-二氟-1-甲基-4-氧代-1H，4H-[1，3]硫氮杂环丁烷并[3，2-α]喹啉-3-羧酸乙酯，总收率23％。     

Basic study for stabilization of w/o/w emulsion and its application to transcatheter arterial embolization therapy

Stabilization of w/o/w emulsion and its application to transcatheter arterial embolization (TAE) therapy are reviewed. W/o/w emulsion was stabilized by making inner aqueous phase hypertonic, addition of chitosan in inner phase, and techniques of phase-inversion with porous membrane. Lipiodol w/o/w emulsion for TAE therapy was prepared by using a two-step pumping emulsification procedure. The procedure is so easy that the emulsion could be prepared even during the surgical operation. The deposition after hepatic arterial administration of the emulsion was detected by an X-ray CT scanner. The concentration of epirubicin hydrochloride (EPI) in liver was increased and its residence was prolonged by encapsulating it in the w/o/w emulsion. The toxic effects of EPI and lipiodol on the normal hepatic cells were reduced. The w/o/w emulsion prepared by us is a suitable formulation for the TAE therapy.     

Rheological study of w/o/w emulsion by a cone-and-plate viscometer: Negative thixotropy and shear-induced phase inversion

The rheological behaviour of a w/o/w emulsion was examined by a cone-and-plate viscometer. Negative thixotropic flow patterns were observed at lower shear rates. This negative thixotropic behavior was more pronounced and the apparent viscosity increased under increased shear rate, prolonged shearing time, or repeated shear. Further shearing, by raising the shear rate or prolonging the shearing time, rapidly increased the shear stress of the emulsion and induced phase inversion. This phase-inverted emulsion was of the w/o type and in a semi-solid state. The energy dissipated by the flow of the emulsion until the occurrence of phase inversion, the kinetic energy of the emulsion at the phase-inversion point, and the impulse applied to the emulsion by the cone of the viscometer were calculated in order to determine the hydrodynamic parameter determining the phase inversion. The impulse applied by the rotating cone was the parameter determining the phase inversion of the emulsion from a w/o/w to a w/o type characterized by being in the semi-solid state. The negative thixotropic flow and the phase inversion of the w/o/w emulsion to the w/o type induced by shearing were explained as being due to the increase in the volume fraction of the oil droplets by entrapment of water molecules and by coalescence of the oil droplets.     

Skin permeation mechanism of aceclofenac using novel nanoemulsion formulation

The aim of the present study was to investigate the skin permeation mechanism of aceclofenac using a novel nanoemulsion formulation. An optimized oil-in-water nanoemulsion of aceclofenac was prepared by the spontaneous emulsification method. The optimized nanoemulsion contained 2% w/w aceclofenac, 10% w/w Labrafil, 5% w/w Triacetin, 35.33% w/w Tween 80, 17.66% w/w Transcutol P and 32% w/w distilled water. The skin permeation mechanism was evaluated by FTIR spectroscopy, DSC thermography, activation energy measurement and histopathological examination. FTIR spectra of skin treated with the nanoemulsion formulation indicated breaking of the hydrogen bond network at the head of ceramides. DSC thermograms indicated that intracellular transport could be a possible mechanism of permeation enhancement and that permeation occurred due to the extraction of SC lipids by the nanoemulsion. The significant decrease in activation energy for aceclofenac permeation across rat skin indicated that the SC lipid bilayers were significantly disrupted (p < 0.05). Photomicrography of skin showed disruption and extraction of lipid bilayers as distinct voids and empty spaces visible in the epidermal region. Overall these findings indicated that nanoemulsions can be successfully used to enhance skin permeation of drugs.     

Release characteristics of brilliant blue from calcium-alginate beads coated with quaternized chitosan

Calcium-alginate beads coated with quaternized chitosan were prepared in a neutral environment, and morphologies were observed by SEM. Optimum conditions for the encapsulation and retention of a model drug (brilliant blue, BB) in acid were obtained from studies of preparation conditions, including alginate and quaternized chitosan concentration, calcium chloride (CaCl2) concentration in the gelling medium and by comparing one-step and two-step preparation methods. Results showed that very high BB encapsulation efficiency (99%, w/w) and low leakage in acid (8%, w/w) was achieved from dry beads when 2.0% (w/v) alginate was dropped into 1.0% (w/v) CaCl2 containing 0.3% (w/v) quaternized chitosan by a one-step method. The release of BB in 0.9% (w/v) NaCl was modulated by coating calcium-alginate with different weight average molecule weight (Mw) and degree of substitution (DS) of quaternized chitosan. A decreased of Mw accelerated the release of BB and a high DS value significantly decreased the release in 0.9% (w/v) NaCl.     

Chemical characterisation of Hoodia gordonii extract

The chemical composition of a solvent extract of Hoodia gordonii termed ‘H. gordonii extract’ has been characterised by hyphenated chromatographic methods and traditional analytical techniques. The extract consists of a mixture of steroid glycosides, fatty acids, plant sterols and polar organic material.High performance liquid chromatography (HPLC) with ultra violet (UV) and mass spectrometric (MS) detection was used to quantify and confirm the identity of a number of steroid glycosides (73.7% w/w) present in the extract. Gas chromatography (GC) with MS and flame ionisation detection (FID) was applied to determine the fatty acid (3.12% w/w) sterol (0.39% w/w) and alcohol (0.03% w/w) content of a saponified sample of the extract. Polar organic material was quantified by gravimetric methodology using C₁₈ SPE separation and was determined to be a minimum of 3% w/w. Moisture content was measured by Karl Fischer coulometric titration (0.81% w/w).The protein content was investigated by sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) with SYPRO Ruby staining and a negative result was determined with a limit of detection of <0.001%w/w of protein per band. The chemical composition of the extract remained stable for 19 months when stored in re-sealable plastic bags at ambient (21–24 °C) temperature and <60% relative humidity.     

Microencapsulation using poly(L-lactic acid). I: Microcapsule properties affected by the preparative technique

Microcapsules were prepared using a poly (L-lactic acid) (L = PLA), mol. wt. 43,200, by an emulsification and solvent evaporation technique. Phenobarbitone (PB) was used as a reference drug, (core to polymer ratio, 1:1). Both the o/w and w/o emulsion system were investigated in order to study microcapsule properties affected by the preparative technique. In the o/w system, dichloromethane (DCM) was used to dissolve L = PLA and PB and the resulting solution was dispersed in 1 per cent aqueous gelatin solution. Subsequent evaporation of the DCM resulted in the formation of microcapsules. PB was found to be poorly encapsulated within microcapsules from this o/w system. PB content in the microcapsules was found to improve using PB saturated aqueous gelatin solution as the continuum. In the w/o system, acetonitrile (AN) was used as a solvent for L-PLA and PB and light liquid paraffin (LLP), containing 2 per cent w/w Span 40, as the continuous phase. PB loading in the microcapsules was found to be very high from this w/o system. Microcapsules from the o/w system were very small compared to microcapsules obtained from the w/o system. The morphology of the microcapsules and the surface properties were found to be affected distinctly by the two techniques. Microcapsules from the o/w system showed a smooth and less porous surface, whereas a highly porous surface containing embedded PB crystals was found in the microcapsules from the w/o system.     

Effect of limonene on the in vitro permeation of nicardipine hydrochloride across the excised rat abdominal skin

The aim of the present investigation was to study the effect of limonene on in vitro permeation of nicardipine hydrochloride across the excised rat abdominal skin from a 2% w/w hydroxypropyl cellulose (HPC) gel. The HPC gel formulations containing 1% w/w of nicardipine hydrochloride and selected concentrations of limonene (0% w/w to 12% w/w) were prepared, and subjected to in vitro permeation of the drug through excised rat abdominal epidermis. The drug content in the gels was found to be uniform and the drug was found to be stable in the HPC gel formulations. The permeation flux of nicardipine hydrochloride across rat epidermis was increased markedly by the addition of limonene to the HPC gels. A maximum flux was observed (246 +/- 1 micrograms/cm2/h) with an enhancement ratio of about 8 when limonene was incorporated at a concentration of 4% w/w. However, there was no further increase in the permeability of nicardipine hydrochloride beyond 4% w/w of limonene. The DSC and FT-IR data indicated that limonene increased the permeability of nicardipine hydrochloride across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that limonene may be useful for enhancing the skin permeability of nicardipine hydrochloride from transdermal therapeutic system containing HPC gel as a reservoir.     

In vitro percutaneous permeability enhancement of nimodipine by limonene across the excised rat abdominal skin

The purpose of the present study was to investigate the effect of limonene on the in vitro permeation of nimodipine across the excised rat abdominal skin from a 2% w/w hydroxypropyl methylcellulose (HPMC) gel drug reservoir system. The HPMC gel formulations containing 1.5% w/w of nimodipine and selected concentrations of limonene (0% w/w to 8% w/w) were prepared, and subjected to in vitro permeation of the drug through excised rat abdominal epidermis. The drug content in the gels was found to be uniform, and the drug was found to be stable in HPMC gel formulations. The flux of nimodipine across rat epidermis was markedly increased by the addition of limonene to the HPMC gels. A maximum flux of nimodipine was observed (203+/-0.6 microg/cm2 x h) with an enhancement ratio of about 5.7 when limonene was incorporated in HPMC gel at a concentration of 4% w/w. However, there was no further increase in the permeability of nimodipine beyond 4% w/w of limonene in the HPMC gel. FT-IR data indicated that limonene increased the permeability of nimodipine across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that limonene is useful for enhancing the skin permeability of nimodipine from transdermal therapeutic systems containing HPMC gel as a reservoir.     

Extraction of berberine from rhizome of Coptis chinensis Franch using supercritical fluid extraction

Supercritical fluid was used to extract berberine from rhizome of Coptis chinensis Franch. The recovery of berberine was compared with various modifiers, i.e. methanol and 95% ethanol with and without surfactant Tween 80, and 1,2-propanediol. The results show that the yield obtained after 3 h extraction with 1,2-propanediol-modified supercritical carbon dioxide was the highest (from 6.91%, w/w at 200 bar to 7.53%, w/w at 500 bar), while that obtained with 95% ethanol modified-supercritical carbon dioxide was the lowest (from 0.15%, w/w at 300 bar to 0.19%, w/w at 600 bar). The recovery of berberine was not improved by adding 5% Tween 80 in supercritical fluid.     

Permeation characteristics of a hydrophilic basic compound across a bio-mimetic artificial membrane

In the present study, the permeation characteristics of a hydrophilic basic compound (HBC) in a bio-mimetic parallel artificial membrane permeability assay (bio-mimetic PAMPA) were investigated in detail. The bio-mimetic PAMPA membrane was constructed on a hydrophobic filter by impregnating a lipid solution consisting of phosphatidylcholine (0.8%, w/w), phosphatidylethanolamine (0.8%, w/w), phosphatidylserine (0.2%, w/w), phosphatidylinositol (0.2%, w/w), cholesterol (1.0%, w/w), and 1,7-octadiene (97.0%, w/w). The pH-permeability curve (pH 3-10), the effect of lipid composition, concentration dependency (0.02-2.00 mM), and inhibition by other cationic compounds, were investigated for several HBCs. Ketoprofen and methylchlorpromazine were also employed as an acidic and a quaternary ammonium compound, respectively. At pH 3-6, the permeability of timolol, a HBC, was higher than expected from the pH-partition hypothesis, especially in the PI-containing membrane, whereas the pH-permeability curve of ketoprofen followed the pH-partition hypothesis. Permeation of HBC was saturable and inhibited by basic and quaternary ammonium compounds. Similar results were also found for methylchlorpromazine. The permeation characteristics of HBC observed in the present study are not usually expected in a passive permeation process across an artificial membrane. The participation of facilitated permeation of cationic species was suggested, in addition to a simple passive diffusion of un-dissociated species. Ion pair transport was suggested as a possible permeation mechanism of cationic species. However, further investigation is necessary to clarify the reason for the permeation characteristics of HBC.