羚羊角塞水溶性蛋白质成分的解热、镇惊和镇痛作用研究

目的:研究羚羊角塞的水溶性蛋白质成分(分子量超过16kDa)的药理作用。方法:用水煎提取和透析法分离羚羊角塞中的水溶性蛋白质,以家兔伤寒杆菌发热法,小鼠戊四氮致惊法、热板法及扭体法研究其解热、镇惊和镇痛作用。结果:羚羊角塞的水溶性蛋白质成分对家兔的解热作用可持续4～5h(P<0.05),并能使戊四氮引起的小鼠惊厥潜伏期和生存期均明显延长(P<0.05,P<0.01),能明显减少酒石酸锑钾引起的小鼠扭体次数(P<0.01)和明显提高小鼠痛阈值(给药后20、30min,P<0.01)。结论:羚羊角塞水溶性蛋白质成分具有解热、镇惊和镇痛作用,是羚羊角塞中的有效部位或有效成分之一。     

正交法优选酒炙川牛膝最佳炮制工艺

目的优选川牛膝的酒炙工艺。方法采用正交设计L9(34),以水溶性成分及杯苋甾酮的含量为考察指标。结果最佳酒炙工艺为饮片加10%的黄酒润透,130℃炒制15min。结论优选得到的工艺是合理的。     

不同采集地土茯苓中(切面红色、白色)总糖及多糖含量分析与体外抗氧化作用

目的:分析测定26个不同采集地土茯苓中(切面红色、白色)总多糖及多糖的含量并探讨其体外抗氧化活性。方法:采用蒽酮-硫酸比色法,比较分析不同产地及不同切面颜色土茯苓中总糖及多糖含量;同时,以抗坏血酸为阳性对照,通过DPPH自由基(1,1-二苯基-2-苦肼基自由基)清除法来评价该药材中总糖与多糖的抗氧化能力。结果:切面红色土茯苓中总糖的质量分数为1.897 3%~11.680 9%,多糖为0.048 0%~1.863 4%;切面白色土茯苓中总糖的质量分数为7.957 5%~81.681 0%,多糖为0.413 2%~7.963 9%,两者含量差异较大;抗氧化结果表明,总糖及多糖均有清除自由基活性,其IC50依次为抗坏血酸(0.033 4 g·L-1)切面红色多糖(0.176 7 g·L-1)切面白色多糖(0.294 9 g·L-1)切面红色总糖(0.354 8 g·L-1)切面白色总糖(0.769 5 g·L-1)。结论:不同切面颜色及不同产地土茯苓药材中总糖及多糖的含量存在显著性差异,其多糖的含量高低与抗氧化作用的强弱不呈正相关。     

超高效液相串联质谱法同时测定保健食品中10种水溶性维生素

目的：建立超高效液相色谱-串联质谱检测方法同时测定保健食品中10种水溶性维生素。方法：样品经过前处理后,采用Waters ACQUITY UPLC HSS T3（2.1×100 mm,1.8μm）色谱柱分离;以0.1%甲酸的甲醇溶液和0.1%甲酸的水溶液为流动相进行梯度洗脱,通过电喷雾离子源多反应监测（MRM）模式进行检测。结果：10种水溶性维生素在6 min内完成分离,线性关系良好（r≥0.997）,方法检出限在5~250μg·kg^-1之间。3个添加水平的回收率和相对标准偏差RSD（n=6）分别为85.9%~109.5%和1.09%~0.79%。结论：该方法简便、快速、准确、灵敏,适用于保健食品中水溶性维生素的测定。     

丹参水溶性成分抗心肌缺血的作用机制

心肌缺血常伴随能量代谢异常、氧化应激、肾上腺素类激素水平异常波动等。作为中医经典的活血化瘀药,丹参已广泛用于各种心肌缺血性疾病的临床治疗,其中水溶性物质为其重要活性成分。综述丹参水溶性成分丹参素、丹酚酸和原儿茶醛等对能量代谢、儿茶酚胺代谢和氧化应激的调节作用,探讨其心血管作用机制。     

In Vitro System to Evaluate Oral Absorption of Poorly Water-Soluble Drugs: Simultaneous Analysis on Dissolution and Permeation of Drugs

Purpose. The aim of the present work was to develop a new in vitro system to evaluate oral absorption of poorly water-soluble drugs by utilizing Caco-2 monolayers. Methods. Caco-2 monolayer was mounted between side-by-side chambers, which enabled the simultaneous assay of dissolution and permeation of drugs (dissolution/permeation system; D/P system). Apical and basal sides of the chamber were filled with buffer solutions. Drugs were applied to the apical side as powder, suspension, or solution, and then, the permeated amounts into the basal side were monitored for 2 h. At the same time, dissolved amounts of drugs at the apical side were detected. The amount of drug applied to the D/P system was based on its in vivo clinical dose. Results. Sodium taurocholate (5 mM, apical side) and bovine serum albumin (4.5% w/v, basal side) increased the permeated amount of poorly water-soluble drugs. Both additives were considered to be effective at mimicking in vivo conditions of intestinal drug absorption. From the correlation between the permeated amount of 13 drugs (% dose/2 h) in the D/P system and their percentage dose absorbed in humans in vivo, this system was found to be useful in evaluating oral absorption of poorly water-soluble drugs. Conclusions. With attempts made to mimic the physiologic conditions of the human GI tract, in vivo oral absorption of drugs was quantitatively assessed in the D/P system in vitro. This system is quite useful to predict the oral absorption of poorly water-soluble drugs after administration as solid dosage forms.     

无定形态药物结晶行为的研究进展

将药物的固体形态由晶态转变成分子无序排列的无定形态,可用于提高难溶性药物溶解度和溶出速率。无定形药物制剂已经成为提高难溶性药物生物利用度的最常用策略之一。目前,已有多种技术方法可将药物从晶态转变为无定形态,其中应用最成熟的技术包括喷雾干燥、热熔挤出技术等,在药物制剂工业中得到广泛的运用。此外,一些新型的技术方法例如3D打印技术和电纺丝技术等近年来也被报道用于无定形态药物的制备。这些不同的制备方法将会对无定形态药物的理化性质产生重要的影响。对无定形态药物制备方法的最新研究进行总结和分析,为无定形态药物的开发提供借鉴。

     

The Combined Effects of Magnesium Oxide and Inulin on Intestinal Microbiota and Cecal Short-Chain Fatty Acids

Constipation is a common condition that occurs in many people worldwide. While magnesium oxide (MgO) is often used as the first-line drug for chronic constipation in Japan, dietary fiber intake is also recommended. Dietary fiber is fermented by microbiota to produce short-chain fatty acids (SCFAs). SCFAs are involved in regulating systemic physiological functions and circadian rhythm. We examined the effect of combining MgO and the water-soluble dietary fiber, inulin, on cecal SCFA concentration and microbiota in mice. We also examined the MgO administration timing effect on cecal SCFAs. The cecal SCFA concentrations were measured by gas chromatography, and the microbiota was determined using next-generation sequencing. Inulin intake decreased cecal pH and increased cecal SCFA concentrations while combining MgO increased the cecal pH lowered by inulin and decreased the cecal SCFA concentrations elevated by inulin. When inulin and MgO were combined, significant changes in the microbiota composition were observed compared with inulin alone. The MgO effect on the cecal acetic acid concentration was less when administered at ZT12 than at ZT0. In conclusion, this study suggests that MgO affects cecal SCFA and microbiota during inulin feeding, and the effect on acetic acid concentration is time-dependent.     

Anti-Inflammatory and Antishock Water-Soluble Polyesters of Glucocorticoids with Low Level Systemic Toxicity

Purpose. The objective of this study was to evaluate the pharmacological activity of glucocorticoid hormones incorporated into the structure of water-soluble carbochain polymers via the esterified 21-CH₂OH group. Methods. Polymer analogs of glucocorticoids were prepared by radical copolymerization of l-vinyl-2-pyrrolidone with cortisol or dexamethasone 21-crotonates and crotonic acid or 2-(diethylamino) ethylcrotonate which served as ionogenic comonomers. Anti-inflammatory, immuno-suppressive and catabolic activities for ionogenic tertiary copolymers and previously prepared non-ionogenic binary copolymers were evaluated in standard animal models. The antishock activity of some of the copolymers was evaluated using the declamping shock model. Results. Water-soluble tertiary copolymers with a steroid content up to 14 mol% and an intrinsic viscosity up to 0.30 dl/g in ethanol were synthesized. It was shown that the copolymers were stable in aqueous solutions at pH 5.2–7.3. All of the polymers studied suppressed inflammatory reactions at the level of free hormones when administered interperitoneally. The antishock activity was considerably higher compared to free steroids. The copolymers, unlike unmodified glucocorticoids, did not influence the physical development of young animals. They also caused much lower thymus hypotrophy than free hormones. No clear effect of the presence and nature of ionogenic units in copolymers on the pharmacological performance of the copolymers was detected. Conclusions. The water-soluble polymers bearing glucocorticoid 21-residues in the side chains retain the anti-inflammatory activity of free steroids and exhibit a higher antishock, a lower immunosuppressive and no catabolic effect.     

5种有“味酸”药性的蔷薇科果实类药材中水溶性有机酸的测定与分析

目的通过测量5种蔷薇科果实类药材(山楂、木瓜、乌梅、金樱子和覆盆子)的p H值及水溶性有机酸含量,探索"味酸"药性下各药材含水溶性有机酸的异同。方法采用直接电位法和电位滴定法测定5种药材的p H值和可滴定总有机酸含量;采用反相高效液相色谱三波长切换法辨识并定量测定水溶性有机酸奎尼酸、苹果酸、莽草酸、柠檬酸、富马酸、原儿茶酸和绿原酸的含量。结果 5种药材p H值从低到高依序为乌梅(2.64)山楂(3.19)木瓜(3.28)覆盆子(4.33)金樱子(5.06)。可滴定总有机酸含量从高到低依序为乌梅(16.2%)山楂(8.39%)木瓜(7.19%)金樱子(3.97%)覆盆子(3.58%)。木瓜和乌梅含有检测的7种有机酸;金樱子未检出绿原酸;覆盆子未检出绿原酸和奎尼酸。各药材中含量较高的有机酸分别是柠檬酸(乌梅1.09%;山楂0.290%;覆盆子0.272%)、莽草酸(木瓜0.753%)和奎尼酸(金樱子0.277%)。数据分析显示,药材p H值与可滴定总有机酸含量呈现良好的负相关(Pearson correlation coefficient为-0.73,P0.01);5种药材中可滴定总有机酸与柠檬酸在含量高低变化上的表现趋向一致。比较5种药材中各有机酸的含量,呈现出单体有机酸谱变化各异。结论该实验对5种药材的水溶性有机酸类成分进行了较为全面分析,为"味酸"中药的重要物质基础系统表征和量化提供方法思路、积累实验资料;也为《中国药典》将柠檬酸作为乌梅、山楂药材的质量指标成分提供依据。