超临界CO2萃取山茱萸成分研究

目的 :对山茱萸超临界CO2 流体萃取物进行研究。方法 :萃取条件为 :压力 15MPa,温度 4 0℃ ,时间2h ,液态CO2 流量 2 2 .0kg·h-1,,采用GC MS技术分析山茱萸CO2 超临界萃取物的化学组成。结果 :超临界CO2流体萃取法得率为 2 .4 2 %。鉴定了其中 31种成分 ,并用面积归一化法测定其相对含量。结论 :超临界CO2 流体萃取物主要成分有 1,2 苯二甲酸二 (1 丁基 2 异丁基 )酯 ,异丙基十四 [烷 ]酸酯等。     

玉米粉水解物作为红霉素发酵培养基的研究

研究了摇瓶试验中玉米粉水解物替代葡萄糖发酵红霉素的最佳培养基组成。用均匀设计法得到发酵基础培养基的最佳配比(wB，％)：玉米粉3．6，黄豆饼粉2．0，玉米浆0．23，碳酸钙0．5，淀粉0．6；用正交试验得到了优化的补混合料配比(％)：玉米粉4．5，黄豆饼粉2．0，硫酸铵1．0，酵母粉2．0；并得到了玉米粉的最适水解条件。30t发酵罐放大实验结果表明，用玉米粉水解物替代葡萄糖作碳源发酵红霉素，发酵单位提高5．8％，综合生产成本降低26．0％。     

Characterizing the influence of structure and route of exposure on the disposition of dithiocarbamates using toluene-3,4-dithiol analysis of blood and urinary carbon disulfide metabolites.

Differences in the toxicities observed for dithiocarbamates have been proposed to result from the influence of nitrogen substitution, oxidation state, and route of exposure. To better characterize the fate of dithiocarbmates in vivoas a function of structure and route of exposure, rats were administered equimolar doses of carbon disulfide (CS2), N-methyldithiocarbamate, pyrrolidine dithiocarbamate, N,N-diethyldithiocarbamate, or disulfiram daily for five days, either po or ip, and sequential blood samples obtained. Protein dithiocarbamates formed by the in vivo release of CS2, parent dithiocarbamate, and protein-bound mixed disulfides were assessed in plasma and hemolysate by measuring toluene trithiocarbonate generated upon treatment with toluene-3, 4-dithiol (TdT). To aid in determining the bioavailability of CS2 from the administered dithiocarbamates, the urinary CS2 metabolites, 2-thiothiazolidine-4-carboxylic acid (TTCA) and 2-thiothiazolidin-4-ylcarbonylglycine (TTCG), were also determined. The levels of TdT-reactive moieties detected depended upon both the compound administered and the route of exposure. Parent dithiocarbamates, with the exception of disulfiram, were eliminated from blood within 24 h; but protein associated TdT-reactive moieties persisted and accumulated with repeated exposure, regardless of the route of exposure. N-Methyldithiocarbamate demonstrated the greatest potential to produce intracellular globin modifications, presumably through its unique ability to generate a methylisothiocyanate metabolite. Urinary excretion of TTCA and TTCG was more sensitive than TdT analysis for detecting dithiocarbamate exposure, but TdT analysis appeared to be a better indicator of in vivo release of CS2 by dithiocarbamates than were urinary CS2 metabolites. These data suggest that CS2 is a more important metabolite, following oral exposure, than are other routes of exposure, e.g., inhalation or dermal. In addition, data also suggest that acid stability, nitrogen substitution, and route of exposure are important factors governing the toxicity observed for a particular dithiocarbamate.     

Disassociation of carbon disulfide-induced depression of flash-evoked potential peak N166 amplitude and norepinephrine levels.

Exposure to organic solvents frequently causes functional impairment of the central nervous system (CNS). One method to examine the effects of solvent exposure on visual function is flash-evoked potentials (FEPs). Greater knowledge of the role of various neurotransmitters in generating FEP peaks would be beneficial for understanding the basis of neurotoxicant-induced changes. FEP peak N166 is influenced by the psychological construct of arousal, which in turn is believed to be influenced by the function of neurons containing norepinephrine (NE). Because of its known effects on both NE and FEPs, we utilized carbon disulfide (CS2) as a means to examine the possible role of NE in modulating the amplitude of FEP peaks N36 and N166. Our hypothesis was that CS2-induced alterations in cortical NE levels would be correlated with changes in FEP peak N36 and N166 amplitudes. Adult male Long-Evans rats were implanted with electrodes over their visual cortex and allowed to recover. To develop peak N166, FEPs were recorded for two days prior to dosing. On the third day, FEPs were recorded prior to dosing, and one group of animals was sacrificed to serve as pretreatment controls. The remaining animals were dosed ip with 0 (corn oil vehicle; 2 ml/kg), 100, 200, or 400 mg/kg CS2. The treated animals were retested at 1, 4, 8, or 24 h after dosing, immediately sacrificed, and samples of the cortex, cerebellum, striatum, and brain stem were frozen for high performance liquid chromatography (HPLC) analysis of monoamine levels. Treatment with CS2 decreased peak N166 amplitude at 1 h, and peak N36 amplitude was depressed at 4 h, relative to the subject's pretreatment values. Peak latencies were increased, and colonic temperature was decreased by treatment with CS2. Exposure to CS2 depressed NE levels in the cortex, brain stem, and cerebellum 4 h after treatment. Conversely, at 4 h, levels of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid were increased in the brain stem and cerebellum, and levels of the DA metabolite homovanillic acid were increased in the brain stem. Levels of serotonin were unaffected by CS2 treatment. There was a slight increase in striatal levels of the serotonin metabolite 5-hydroxyindole acetic acid at all times after treatment with CS2. There was no apparent association between the decreases in NE levels and the reductions in amplitudes for peaks N36 and N166. The neurochemical mechanism for CS2-induced reductions in FEP peak amplitudes remains to be determined.     

Synthesis of 3H and 14C labeled (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐indol‐2‐one,maxipost™. An agent for post‐stroke neuroprotection

The syntheses of tritium labeled (S)‐3‐(5‐chloro‐2‐[OC³H₃]methoxyphenyl‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐1H‐indol‐2‐one, and carbon‐14 (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐[2,3‐¹⁴C₂] indol‐2‐one are reported. The ³H‐labeled compound was prepared in a two‐step synthesis from C³H₃I. The final product was purified via chiral HPLC to yield the desired enantiomer in a 4% radiochemical yield and a specific activity of 60 Ci/mmol. The ¹⁴C‐labeled compound was prepared in a four‐step synthesis from diethyl [carboxylate‐¹⁴C₁,₂] oxalate. The final product was purified via chiral HPLC to yield the desired enantiomer in a 20% radiochemical yield and a specific activity of 28.4 μCi/mg. Copyright © 2002 John Wiley & Sons, Ltd.     

Efficient synthesis of [11C]befloxatone,a selective radioligand for the in vivo imaging of MAO‐A density using PET

Carbon‐11 labelled befloxatone ((5R)‐5‐(methoxymethyl)‐3‐[4‐[(3R)‐4,4,4‐trifluoro‐3‐hydroxybutoxy]phenyl]‐2‐oxazolidinone) is a reversible and selective monoamine oxidase‐A (MAO‐A) inhibitor and appears to be a new potent PET tracer for the in vivo imaging of MAO‐A density. In this paper, the radiosynthesis of befloxatone was investigated and orientated towards the preparation of multi milliCuries of radiotracer. Typically, using no‐carrier‐added [¹¹C]phosgene, 150–300 mCi (5.55–11.10 GBq) of [¹¹C]befloxatone was obtained within 20 min of radiosynthesis (including HPLC purification) with specific radioactivities ranging from 500 to 2000 mCi/µmol (18.5–74.0 GBq/µmol). The high efficiency of these radiosyntheses allows for multi‐injection protocols and kinetic approaches for absolute quantification of the tracer. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of tritium and carbon‐14 labelled NNC 61‐4655: a potent dual‐acting PPARα and PPARγ agonist

The synthesis of the potent dual‐acting PPARα and PPARγ agonist NNC 61‐4655 labelled with tritium and carbon‐14 is reported. Tritium labelled NNC 61‐4655 was obtained in three steps with introduction of tritium through catalytic tritium‐halogen exchange of an aryl bromide precursor. This provided [³H]NNC 61‐4655 in 39% overall radiochemical yield with a specific activity of 49 Ci/mmol. Carbon‐14 labelled NNC 61‐4655 was obtained in five steps starting from bromo[1‐¹⁴C]acetic acid. The synthetic sequence, which included a Horner–Wadsworth–Emmons olefination and a Mitsunobu alkylation, provided [¹⁴C]NNC 61‐4655 in 33% overall radiochemical yield with a specific activity of 57.4 mCi/mmol. Copyright © 2003 John Wiley & Sons, Ltd.     

Engineering analysis of diamond-like carbon coated polymeric materials for biomedical applications

Diamond-like carbon (DLC) films have received much attention recently owing to their properties, which are similar to diamond: hardness, thermal conductivity, corrosion resistance against chemicals, abrasion resistance, good biocompatibility, and uniform flat surface. Furthermore, DLC films can be deposited easily on many substrates for wide area coat at room temperature. DLC films were developed for applications as biomedical materials in blood contacting-devices (e.g., rotary blood pump) and showed good biocompatibility for these applications. In this study, we investigated the surface roughness by Atomic Force Microscopy (AFM) and Hi-vision camera, SEM for surface imaging. The DLC films were produced by radio frequency glow discharge plasma decomposed of hydrocarbon gas at room temperature and low pressure (53 Pa) on several kinds of polycarbonate substrates. For the evaluation of the relation between deposition rate and platelet adhesion that we investigated in a previous study, DLC films were deposited at the same methane pressure for several deposition times, and film thickness was investigated. In addition, the deposition rate of DLC films on polymeric substrates is similar to the deposition rate of those deposited on Si substrates. There were no significant differences in substrates' surface roughness that were coated by DLC films in different deposition rates (16-40 nm). The surface energy and the contact angle of the DLC films were investigated. The chemical bond of DLC films also was evaluated. The evaluation of surface properties by many methods and measurements and the relationship between the platelet adhesion and film thickness is discussed. Finally, the presented DLC films appear to be promising candidates for biomedical applications and merit investigation.     

BF3 etherate catalysed formation of [11C]methyl esters: a novel radiolabelling technique

A novel way of preparing ¹¹C labelled methyl esters using [¹¹C]methanol and either BF₃ etherate or trimethylsilyl chloride as catalyst was investigated. Radiochemical yields with BF₃ etherate were between 30 and 33% for [¹¹C]methyl benzoate and less than 1% for [¹¹C]methyl thio salicylate. No [¹¹C]methyl ester formation could be observed with trimethylsilyl chloride for all compounds investigated. This method is an alternative to using [¹¹C]methyl iodide in the presence of a base. It is particularly suited for carboxylic acids bearing functional groups which would compete for [¹¹C]methyl iodide, thus eliminating the need to introduce protecting groups. However, o‐anisic acid formed [¹¹C]methyl salicylate in 33–30% decay corrected radiochemical yield due to hydrolytic cleavage of the methyl ether, and none of the desired [¹¹C]methyl 2‐methoxy benzoate could be obtained. When salicylic acid was used as starting material, [¹¹C]methyl salicylate could only be obtained in 5–8% decay corrected radiochemical yield. Copyright © 2004 John Wiley & Sons, Ltd.     

A rapid one‐step radiosynthesis of the β‐amyloid imaging radiotracer N‐methyl‐[11C]2‐(4′‐methylaminophenyl)‐6‐hydroxybenzothiazole ([11C]‐6‐OH‐BTA‐1)

The promising β‐amyloid PET imaging agent, [¹¹C]‐6‐OH‐BTA‐1, has been radiolabelled in one step using [¹¹C]‐methyl triflate. No protection of the 6‐hydroxy group is required, greatly simplifying the synthetic method. The reaction may be carried out in solution or by the captive solvent ‘loop’ method. Copyright © 2004 John Wiley & Sons, Ltd.