带形蜈蚣藻硫酸多糖的提取、分析及其抗病毒活性

目的提取带形蜈蚣藻硫酸多糖,研究其理化性质和抗病毒活性。方法用热水浸提、乙醇沉淀法提取带形蜈蚣藻硫酸多糖、再经DEAE C-52纤维素离子交换柱层析得到2个较纯组分。并对其进行了单糖组成和硫酸基含量等理化性质分析。采用细胞病变(cytopathic effect,CPE)抑制法和四甲基偶氮唑盐(MTT)比色法,研究带形蜈蚣藻多糖的抗病毒活性。结果带形蜈蚣藻多糖主要由半乳糖组成,还含有少量的葡萄糖、木糖等,其硫酸基含量达到15%以上;该多糖具有较好的抗病毒活性,其中经提纯的两个组分抗HSV-1对细胞病变的半抑制浓度(IC50)分别为7.81,3.91μg.mL-1,选择(指数)SI值分别大于128,256。结论带形蜈蚣藻硫酸多糖抗CoxB3和HSV-1病毒活性均比较好。     

木贼麻黄多糖的提取及体外抗氧化活性研究

目的 优化木贼麻黄多糖的提取工艺,初步研究木贼麻黄多糖的体外抗氧化活性。方法 采用热水浸提法提取木贼麻黄多糖,利用单因素试验结合响应面法对提取条件进行优化,并研究木贼麻黄多糖的体外抗氧化活性。结果 木贼麻黄多糖的最佳提取条件为：提取时间2.5 h,提取温度73℃,液料比25∶1,在此条件下多糖提取率为（5.57±0.072）%。木贼麻黄多糖对DPPH自由基和羟基自由基具有较强的清除能力,IC₅₀分别为703.9 μg·mL^-1和2 135.1 μg·mL^-1;对超氧阴离子自由基具有一定的清除能力,对Fe³⁺有一定的还原能力。结论 该提取工艺能较好地提取木贼麻黄多糖,所得木贼麻黄多糖具有一定的体外抗氧化能力,但活性低于同浓度的维生素C。     

松茸不同提取部位的体外抗肿瘤作用

摘 要 目的： 研究松茸不同提取部位的体外抗肿瘤活性。 方法: 采用MTT法测定松茸乙醇提取物各部位及多糖部位对HepG-2细胞、Hela细胞和MCF-7细胞的抑制作用;采用流式细胞术检测多糖部位诱导HepG-2细胞和Hela细胞凋亡的作用。结果:松茸多糖部位体外对3种肿瘤细胞的IC₅₀分别为53.77μg·ml^-1(HepG-2)、40.04 μg·ml^-1(Hela)、100.65 μg·ml^-1(MCF-7),抑制作用均优于其他各部位,且对HepG-2细胞和Hela细胞抑制作用呈现良好的时间与浓度依赖性;松茸多糖部位能诱导HepG-2细胞和Hela细胞凋亡。结论: 松茸多糖部位能显著抑制HepG-2和Hela等肿瘤细胞的生长,具有诱导凋亡的作用,为松茸抗肿瘤的主要活性部位。     

山药多糖RDPS-I的结构分析及抗肿瘤活性

目的研究山药多糖的化学结构和抗肿瘤活性。方法用水提取山药块茎粗多糖,经Sevag反复脱蛋白8次,透析后经DEAE-cellulose及Sephadex G-100柱色谱纯化得山药多糖RDPS-I。经完全酸水解、部分酸水解,用PC,GC,IR,高碘酸氧化,Smith降解,甲基化分析,¹HNMR及¹³CNMR等研究山药多糖的化学结构。并用小鼠移植性实体瘤研究了RDPS-I的体内抗肿瘤作用。结果RDPS-I的分子量为41 000,比旋光度为［α］²⁰_D=+188.4°(c 0.80,H₂O),特性粘度为［η］=16.48×10^-3(g·mL^-1)。RDPS-I是由葡萄糖、甘露糖和半乳糖以1∶0.4∶0.1的摩尔比组成,以α-D-(1→3)-Glcp为主链,在6-O位有α-D-(1→2)-Manp-β-D-1)-Galp支链的杂多糖。RDPS-I对移植性黑色素B16和Lewis肺癌有很强的抑制作用。结论RDPS-I是由葡萄糖、甘露糖和半乳糖构成的杂多糖,有很强的体内抗肿瘤活性。     

马尾松花粉硫酸酯化多糖对大鼠主动脉平滑肌细胞 [Ca2+]i调控及增殖的影响

目的 研究马尾松花粉多糖PPM60-A及其硫酸酯化物SPPM60-A对大鼠动脉平滑肌细胞 [Ca²⁺]_i调控及增殖的影响。方法 常规水提醇沉法制备马尾松花粉多糖,Sephacryl S-400HR色谱分离得PPM60-A,氯磺酸-吡啶法得硫酸酯化物SPPM60-A,酯化度为1.28。酶解法分离制备大鼠动脉平滑肌细胞,测定酯化前后多糖对其胞内 [Ca²⁺]_i和细胞增殖的影响。结果 PPM60-A和SPPM60-A均可以降低 [Ca²⁺]_i,抑制高K⁺和去甲肾上腺素（NE）诱导的钙离子升高,降低高K⁺引起的钙离子水平上升,对NE诱导的血管主动脉平滑肌细胞增殖具有显著的抑制作用。PPM60-A作用效果好于SPPM60-A。结论 PPM60-A及SPPM60-A均能抑制细胞外Ca²⁺内流,抑制血管平滑肌细胞增殖。     

苯甲酰胺类衍生物的合成及扩血管活性

报道了22个苯甲酰胺类衍生物的合成,其中大多数化合物有不同程度的扩血管活性,化合物H_1,11,17,E_1,3对去甲肾上腺素[NE](10^-7mol·L^-1)引起的大鼠主动脉条收缩的抑制作用明显优于先导物N-(4-甲氧基苯甲酰基)-N′-肉桂基哌嗪,化合物H_7,15,E₇对85.7mmpL·L^-1KCl引起的大鼠主动脉条收缩有明显的抑制作用,进一步钾通道实验表明E1可能为ATP敏感型钾通道开放剂。并初步分析了此类化合物的构效关系。     

氯喹和硫酸羟氯喹对SARS-CoV-2体外抗病毒活性的差异研究

目的 通过改变药物与病毒引入的先后顺序，探讨氯喹与硫酸羟氯喹对严重急性呼吸综合征冠状病毒2（SARSCoV-2）不同变体（Prototype、Beta、Delta、Omicron）的体外抗病毒活性。方法 预防研究：Vero E6细胞用氯喹或硫酸羟氯喹（200.00、150.00、100.00、50.00、16.70、5.55、1.85、0.62、0.21μmol·L^-1）孵育1h，加入病毒附着2h，去除病毒-药物混合物，用新鲜培养基培养细胞直到实验结束；治疗研究：Vero E6细胞中加入病毒吸附2h，去除病毒，用含氯喹或硫酸羟氯喹的培养基培养细胞直到实验结束；全时研究：Vero E6细胞用药物孵育1h，加入病毒附着2h，去除病毒-药物混合物，用含药物的培养基培养细胞直到实验结束。培养72h后显微镜下观察细胞是否变圆脱落判断细胞病变情况，计算半数效应浓度（EC₅₀）及药物选择指数（SI）。结果 2种药物对于SARS-CoV-2的预防效果较差；氯喹和硫酸羟氯喹在治疗和全时处理下均表现出良好的抗病毒活性，其中硫酸羟氯喹的EC₅₀小于氯喹，SI大于氯喹，抗病毒效果较氯喹更优越。在治疗和全时处理条件下，氯喹（EC₅₀＝0.904μmol·L^-1）和硫酸羟氯喹（EC₅₀＝0.143μmol·L^-1）对Omicron变异株抗病毒效果较其他变种更明显。结论 氯喹和硫酸羟氯喹在治疗和全时处理下均表现出良好的抗病毒活性，且2种药物对Omicron变异株的活性高于其他变种。     

牛膝多糖硫酸酯体外和体内抗艾滋病病毒作用

牛膝多糖硫酸酯(Achyranthes bidentata polysaccharide sulfate，ABPS)为牛膝多糖经硫酸酯化修饰后获得的产物，其结构清楚、理化性质稳定及分子质量小，具有抗单纯疱疹病毒、柯萨奇病毒和乙型肝炎病毒等作用。本文研究其在体外和体内的抗艾滋病病毒1型(human immunodeficiency virus type 1，HIV-1)活性。体外采用 ³H掺入法和酶联免疫吸附法测定ABPS对HIV-1逆转录酶和整合酶的活性，其半数抑制浓度(50% inhibiting concentrations,IC₅₀)分别为(2.948±0.556) μmol·L^-1和(0.155±0.030) μmol·L^-1， 但25 μmol·L^-1 ABPS对HIV-1蛋白酶无效。ABPS在MT-4细胞培养内对HIV-1实验病毒株IIIB和在人外周血单核细胞培养内对AZT耐药病毒株的急性感染有较强的抑制作用， 但在HIV-1 IIIB慢性感染的H9细胞培养中则无效。血清药理学研究表明，单次腹腔注射大鼠ABPS 125 mg·kg^-1或连续腹腔注射小鼠ABPS 3 mg·kg^-1(qd×20)后鼠血清在MT-4细胞培养内对HIV-1 P24抗原都有抑制作用，但口服ABPS生物利用度低，灌胃大鼠ABPS 2 g·kg^-1或灌胃小鼠ABPS 300 mg·kg^-1无效。实验结果提示ABPS有抗HIV-1作用，有可能用于防治HIV-1感染，值得进一步研究。     

依布硒啉衍生物对白三烯B4生物合成抑制作用及其构效关系

目的：研究一系列依布硒啉衍生物对白三烯B₄生物合成的影响,并探讨其构效关系。方法：高效液相色谱法测定白三烯B₄。结果：依布硒啉的磺酰胺类似物以及N-芳香环取代的磺酰胺衍生物对白三烯B4生物合成具有抑制作用,其IC₅₀在10^-5～10^-6 mol.L^-1之间,并存在一定的构效关系。结论：磺酰胺基团上的酸性氢原子是关键因素,它的存在可以形成分子内氢键,从而使化合物具有活性。     

不同来源麒麟菜多糖的提取分离和结构比较△

目的 从不同来源麒麟菜中提取分离多糖,分析其理化性质,比较其结构差异。 方法 将6种麒麟菜依次采用冷水和80℃热水提取,提取液经乙醇沉淀、透析及浓缩冻干后获得麒麟菜多糖;分别采用硫酸-苯酚法、Folin-酚法、离子色谱法 (IC)、高效液相色谱法 (HPLC) 等对其总糖、蛋白质、硫酸根含量、分子质量和单糖组成等理化性质进行分析,并采用傅里叶变换红外光谱(FTIR)和核磁共振碳谱(13C-NMR)对其结构进行比较。 结果 从6种麒麟菜中提取获得12种硫酸多糖,其得率在20%~35%之间,其总糖、蛋白质和硫酸根含量分别在55%~75%,2.4%~8.9%和19.9%~35.1%之间,多糖分子量在238~861kDa之间。单糖组成分析表明,各多糖主要由半乳糖以及少量葡萄糖或者木糖组成。EMP-C,EMI-C,EST-C,ESI-C,EDT-C,EST-H,ESI-H,EDT-H主要为ι -卡拉胶,EMP-H,EMI-H,EGH-H,EGH-C主要为κ-卡拉胶。结论 不同来源麒麟菜多糖的结构不同,为不同结构卡拉胶藻源的选择提供了重要参考。     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

欧洲刺柏（Juniper）

活性成分与药理作用欧洲刺柏药用部位是其浆果，具有促水排泄、防腐、抗胃肠胀气和抗风湿作用，还可改善胃功能。用作促水排泄药可增加尿量（水丢失），但不增加钠排泄。成分萜品烯-4-醇可增加肾小球滤过率，但刺激肾。欧洲刺柏浆果对单纯疱疹病毒体外显示抗病毒活性，并具抗真菌活性。动物实验显示，欧洲刺柏浆果提取物具有堕胎、抗生育、抗炎、抗胚胎植入、降血压、升血压和降血糖作用。欧洲刺柏浆果油具有兴奋子宫的活性，以及利尿、胃肠道抗菌和刺激作用，该油对平滑肌有阻止解痉作用。     

Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol. Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects. Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing. In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.     

Oral Presentations (LDD, LPES, LNM, LPAT, LNT, LPPT, LPM)

Probiotic microorganisms have been shown to provide specific health benefits when consumed as food supplements or as food components. The main problem of such products is the poor survival of the probiotic bacteria in the low pH of gastric fluid. However the use of synthetic excipients for enteric coating to prevent the exposure of microorganisms to gastric fluid is limited in food supplementary industry. Therefore the aim of this study was to develop an enteric coating formulation containing shellac as a natural polymer. Shellac possesses good resistance to gastric juice; the major disadvantage of this polymer is its low solubility in the intestinal fluid [1, 2]. Thus films containing different ratios of shellac and water-soluble polymers (sodium alginate, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidon (PVP)) or plasticizers (glycerol and glyceryl triacetate (GTA)) were prepared in order to analyse the films’ melting temperatures (T_m), the changes in enthalpy (ΔH), their capability of taking up water, and their solubility in different media. The release characteristics of the films were studied by loading pellets with Enterococcus faecium M74 and coating them with formulations containing different amounts of shellac and polymer or plasticized shellac. Using dissolution tests, performed according to USP XXXI paddle method, the resistance of the coatings to simulated gastric fluid (SGF, pH 1.2) and the release of cells in simulated intestinal fluid (SIF, pH 6.8) was investigated.The trials showed that an increasing amount of plasticizer results in a decrease of T_m and ΔH of the films whereat glycerol had a superior plasticization effect to GTA. The compatibility of films made of water-soluble polymers and shellac was also concentration dependent. HPMC and PVP showed superior compatibility with shellac compared to sodium alginate, since films containing shellac and more than 10% [w/w] sodium alginate tended to separate into two phases. In the end five formulations containing shellac and either 5% [w/w] glycerol, 10% [w/w] PVP, 20% [w/w] PVP, 10% [w/w] HPMC, or 5% [w/w] sodium alginate emerged as feasible for enteric coating purposes.