应用大孔树脂吸附分离技术制备地锦草总黄酮的研究

目的研究大孔树脂D_A201和D₁₀₁富集地锦草总黄酮的工艺条件和参数。方法以总黄酮含量为指标,采用正交试验设计,考察D_A201和D₁₀₁富集地锦草总黄酮的工艺条件。用分光光度法测定总黄酮含量。结果D_A201精制的最佳工艺为:90 mL浓度约0.65 mg·mL^-1的溶液(pH 7)上柱,吸附流速2 BV·h^-1,洗脱剂为40%乙醇(pH 7),洗脱流速2 BV·h^-1。D₁₀₁精制的最佳工艺为:100 mL浓度约0.65 mg·mL^-1溶液(pH 7)上柱,吸附流速4 BV·h^-1,洗脱剂为40%乙醇(pH 9),洗脱流速2 BV·h^-1。通过D_A201和D₁₀₁精制工艺,平均吸附率分别为83.38%和88.57%,平均洗脱率分别为89.28%和87.21%,洗脱液干燥后的总固物中总黄酮平均含量分别为14.48%和20.18%,分别高于原上样液总固物黄酮含量(8.49%和8.71%)。结论D_A201和D₁₀₁对地锦草总黄酮都有良好吸附分离性能,而D₁₀₁综合性能更好。     

番泻叶提取物的吸湿性及辅料对其影响的研究

目的:研究番泻叶提取物的吸湿性,探讨辅料对番泻叶提取物吸湿性的影响。方法:采用粉末吸湿法,测定样品的吸湿率;以平均吸湿速度、吸湿加速度、吸湿初速度、临界相对湿度等吸湿参数为指标,考察番泻叶提取物的吸湿性及辅料对其的影响。结果:辅料均不同程度地降低了番泻叶提取物的平均吸湿速度,其中乳糖的作用最强;但乳糖对番泻叶提取物的临界相对湿度几乎没有影响。结论:辅料的合理使用可以改善番泻叶提取物的吸湿性。     

指纹图谱的一种定性定量研究新方法：总量统计矩分析法

本文运用了统计矩原理阐明并建立中药复方多成分指纹图谱定性定量分析法：总量统计矩方法。包括4个参数： ① 总零阶矩AUC_T； ② 总响应率AUCPW_T； ③ 总量一阶矩MCRT_T，亦总量中心矩或总量平均保留时间，用_T表示； ④ 总体二阶矩VCRT_T，亦为平均保留时间方差，用²_T表示。AUC_T能用于中药复方指纹图谱定量分析，AUCPW_T、MCRT_T、VCRT_T能用于中药复方指纹图谱定性分析。以此法研究不同产地大黄醇浸膏成分HPLC指纹图谱，得总量统计矩参数：AUC_T为3.273×10⁸ μV·s；AUCPW_T为2.286×10⁶ μV·s·mg^-1；MCRT_T为33.50 min； VCRT_T为484.4 min²；浓度C_T为143.2 mg·mL^-1。本法具有加合运算的特征，能消除溶剂干扰，获得纯品的总量统计矩参数；具偶联性，能与多维向量偶联构成多维曲线中心矩及偏差分析。     

莫达非尼在小鼠体内的药动学-药效学联合研究

对莫达非尼 (modafinil, MOD) 在小鼠体内的药动学和药效学进行联合研究, 以阐明其关联性, 为临床合理用药提供依据。以莫达非尼120 mg·kg⁻¹对小鼠灌胃给药, 采集给药后不同时间点血浆样本, 用HPLC检测血浆药物浓度, 分析平均血药浓度经时变化并计算药动学参数。以小鼠自主活动计数为药效学指标, 观测MOD 120 mg·kg⁻¹灌胃给药后不同时间段内小鼠自主活动量 (计数) 的变化, 分析与血浆药物浓度变化的相关性。结果显示, MOD在小鼠体内药动学过程符合二室模型, t_1/2α, t_1/2β, t_max, C_max, AUC_0−∞分别为0.42 h, 3.10 h, 1.00 h, 41.34 mg·L⁻¹和142.22 mg·L⁻¹·h。MOD使小鼠自主活动明显增多, 持续约4 h, 且与血浆药物浓度呈同步变化, 二者间存在明显的相关性。     

中性盐和碱性盐胁迫对黑果枸杞种子萌发及幼苗生长的影响

在中性盐(NaCl)和碱性盐(Na₂CO₃)胁迫下,对采自河西走廊黑河中游的黑果枸杞进行种子萌发及幼苗生长试验,测定了发芽率(G_r)、发芽势(G_v)、发芽指数(G_I)、活力指数(V_I)和相对盐害率及幼苗的组织含水量、可溶性蛋白质含量、叶绿素含量、电导率、丙二醛含量和POD含量等指标。结果表明,黑果枸杞种子萌发的NaCl、Na₂CO₃浓度的临界值分别是50 mmol·L^-1和2.5 mmol·L^-1,极限值分别是300 mmol·L^-1和100 mmol·L^-1;在NaCl和Na₂CO₃胁迫下,发芽率分别为69.17%和71.67%;幼苗组织含水量分别由对照的88.97%降低到56.17%、70.27%;可溶性蛋白质含量最大值分别为7.09%、7.73%;叶绿素含量分别由对照的1.27 mg·g^-1降到0.78 mg·g^-1、0.92 mg·g^-1;电导率分别由对照的25.63%增加到64.77%、74.8%;丙二醛含量分别由对照的1.5 μmol·g^-1增加到6.9、6.5 μmol·g^-1;POD活性分别由对照的380.4 U·g^-1·min^-1降低到139.2 U·g^-1·min^-1、192.7 U·g^-1·min^-1。黑果枸杞是盐生植物,低浓度的盐促进萌发,高浓度的抑制萌发;碱性盐更适合其生长;黑果枸杞幼苗在盐胁迫下的生理响应及生态适应综合表现出黑果枸杞更适于碱性盐生长。     

水溶性金属卟啉的合成、表征及其清除有毒活性氧的研究

目的合成并结构表征了4种水溶性金属卟啉配合物［5，10，15，20-四［4-(4′-吡啶-1)丁氧基苯基］金属卟啉溴化盐［锌卟啉(I)、铜卟啉(II)、锰卟啉(III)和钴卟啉(IV)］，作为抗活性氧(O^-₂，H₂O₂，HO·)模拟酶。方法 核黄素-蛋氨酸光照测其清除O^-₂作用，H₂O₂氧化Vit C法测其催化H₂O₂的分解，Fenton-苯甲酸钠荧光法测其对HO·清除作用，小鼠肝匀浆法测其抗脂质过氧化作用。结果1.0×10^-5~1.0×10^-6 mol·L^-1均具有良好的清除O^-₂作用；1.5×10^-6~1.0×10^-6 mol·L^-1均具有分解H₂O₂作用；2.0×10^-8~1.0×10^-8 mol·L^-1均具有清除HO·的功能；1.0×10^-7 mol·L^-1均可使脂质过氧化产物明显减少。结论合成4种水溶性金属卟啉配合物可作为抗多种活性氧(O^-₂，H₂O₂，HO·)模拟酶。     

莨菪碱衍生物与M胆碱受体相互作用的构效关系

本文研究了一系列东莨菪碱衍生物对³H-QNB与大鼠脑M受体特异结合的影响。并通过比较它们的IC₅₀(用结合实验),药物—受体相互作用的解离常数K_B(抗乙酰胆碱引起的回肠收缩)以及抗震颤和抗匹罗卡品引起小鼠流涎的ED₅₀,分析了它们的构效关系。结果表明,K_B值与IC₅₀有很好的相关性(r=0.977),其线性回归的斜率为1.047;IC₅₀与抗震颤作用的ED₅₀之间相关性差,而log IC₅₀/ED₅₀值与它们的分配系数(logP)相关好(r=0.971),10号化合物的分配系数最大,中枢作用的选择性也最强。抗流涎ED₅₀与IC₅₀的相关系数为0.827。     

TPPS4的电化学分析法，TPPS4和BSA的相互作用以及环糊精对二者作用体系影响的荧光法研究

目的确立一种快速、准确检测水溶性卟啉(TPPS₄)的分析方法,从而进一步了解水溶性卟啉和牛血清白蛋白(BSA)之间相互作用的机制。方法采用电化学法对TPPS₄的极谱伏安行为进行了研究,同时采用电化学法、荧光法和紫外法对TPPS₄与BSA之间的相互作用分别进行了研究。3种方法相互辅证使得试验结果更加可靠。结果在底液NaH₂PO₄-Na₂HPO₄缓冲液(pH 7.18)中,TPPS₄在-0.70 V(vs SCE)处有一个稳定而灵敏的还原峰,其峰电流与TPPS₄浓度在1.0×10^-7～1.0×10^-5 mol·L^-1有良好的线形关系(r²=0.998 3,0.999 3),检测限LOD为3.0×10^-8 mol·L^-1。平均标准回收率为99.59%,精密度较好,RSD为0.56%(n=5)。在NH₄Cl-NH₃·H₂O缓冲液(pH 9.05)中,实验结果表明BSA与TPPS₄相互作用生成1∶1的TPPS₄-BSA超分子体系。另外,加入环糊精体系后,磺丁醚-β-CD(SBE-β-CD)和羟丙基-β-CD(HP-β-CD)均能促进TPPS₄与BSA发生反应。结论建立了一种简单、快速、准确的水溶性卟啉四-(4-磺基苯)卟啉(TPPS₄)的电化学分析方法。卟啉类药物被环糊精包合后更容易与人体内的蛋白质进行作用,环糊精在卟啉类药物的控制、释放中具有重要的作用和意义。     

小儿宝泰康颗粒对呼吸道病毒感染的抗病毒作用研究

目的 观察小儿宝泰康颗粒对呼吸道合胞病毒和腺病毒感染细胞的抑制作用,以便为呼吸道病毒感染的治疗提供新的药物。方法 通过细胞培养技术观察不同浓度的小儿宝泰康颗粒对HEp-2细胞的细胞毒作用,采用MTT法并结合CPE法检测病毒感染细胞存活率和病毒抑制率,以利巴韦林作为阳性药物对照,评价该药物对呼吸道合胞病毒和腺病毒感染细胞的抗病毒活性。结果 小儿宝泰康颗粒对HEp-2细胞的半数细胞毒性浓度（TC₅₀）为4.4 mg·mL^-1,对呼吸道合胞病毒的半数有效浓度（EC₅₀）为2.03 mg·mL^-1,而腺病毒的EC₅₀为0.65 mg·mL^-1,抗病毒指数分别为2.17和6.75。在对两种病毒的直接灭活作用中,EC₅₀分别为4.13和8.99 mg·mL^-1。阳性对照药物病毒唑在128 g·mL^-1时,对呼吸道合胞病毒和腺病毒的抑制率分别为92.7%和80.16%。结论 小儿宝泰康颗粒是一种对呼吸道合胞病毒和腺病毒感染有抗病毒作用的药物,有临床应用前景和进一步研究的价值。     

pH响应纳米载药系统DOX@MIL-101(Fe)-NH2/HA的制备及靶向抗肿瘤作用研究

目的 制备透明质酸(hyaluronan acid，HA)修饰的纳米金属有机框架MIL-101(Fe)-NH₂载药系统，并进行体外抗肿瘤活性评价。方法 采用溶剂热法制备MIL-101(Fe)-NH₂，通过物理吸附法制备HA修饰载阿霉素的DOX@MIL-101(Fe)- NH₂/HA(DMNH)。并利用扫描电子显微镜、X射线衍射仪、氮气吸附-脱附法等对所合成材料及载药系统进行表征。采用透析法考察了载药系统的体外释药行为，并利用激光共聚焦显微镜观察HepG2细胞对其摄取情况。结果 MIL-101(Fe)-NH₂形貌为规则的正八面体，比表面积和粒径分别为1 061.45 m²·g^-1和200 nm。载药后DMNH的尺寸均一，比表面积为205.84 m²·g^-1，粒径为300 nm。MIL-101(Fe)-NH₂的最佳载药率为65.3%，根据药物释放曲线，从装有阿霉素的MIL-101(Fe)-NH₂载药体系(DMN)、DMNH中释放阿霉素显示出时间和pH依赖性。细胞摄取试验结果显示DMNH较其他组别可以运输更多的阿霉素进入HepG2细胞。细胞毒性的结果证实在相同的药物浓度下，DMNH表现出更高的肿瘤细胞杀伤效率。结论 本研究制备的DMNH载药系统结构稳定、载药量和释药效率高，同时具有优异的肿瘤细胞靶向性及pH响应释放特性，在抗肿瘤药物靶向传输方面具有应用前景。     

Behavior of Moisture Gain and Equilibrium Moisture Contents (EMC) of Various Drug Substances and Correlation with Compendial Information on Hygroscopicity and Loss on Drying

The behavior of moisture gain and equilibrium moisture content (EMC) was determined for 30 drug substances at relative humidities (RH) ranging from 11% to 93%. Based on the results, the drugs were categorized into different classes, following the classification system proposed by Callahan et al. About 23 fell under Class-I (nonhygroscopic), four under Class-II (slightly hygroscopic), and three under Class-III (moderately hygroscopic). Most of the Class-III drugs converted from solid to liquid state at >75% RH, and the moisture increase was more than 40% above 90% RH. However, the moisture increase was comparatively much smaller at humidities < 40%–50%. Hence, no drug could be categorized in Class-IV (very hygroscopic), where gain of moisture is generally higher even at lower humidities. The results were correlated to the statements given in the compendia on hygroscopicity, and also the values of loss on drying (LOD). The study suggests that there is a need to rationalize the pharmacopoeial information.     

Behavior of moisture gain and equilibrium moisture contents (EMC) of various drug substances and correlation with compendial information on hygroscopicity and loss on drying

The behavior of moisture gain and equilibrium moisture content (EMC) was determined for 30 drug substances at relative humidities (RH) ranging from 11% to 93%. Based on the results, the drugs were categorized into different classes, following the classification system proposed by Callahan et al. About 23 fell under Class-I (nonhygroscopic), four under Class-II (slightly hygroscopic), and three under Class-III (moderately hygroscopic). Most of the Class-III drugs converted from solid to liquid state at > 75% RH, and the moisture increase was more than 40% above 90% RH. However, the moisture increase was comparatively much smaller at humidities < 40%-50%. Hence, no drug could be categorized in Class-IV (very hygroscopic), where gain of moisture is generally higher even at lower humidities. The results were correlated to the statements given in the compendia on hygroscopicity, and also the values of loss on drying (LOD). The study suggests that there is a need to rationalize the pharmacopoeial information.     

Behavior of Hygroscopic Pharmaceutical Aerosols and the Influence of Hydrophobic Additives

The high temperature and relative humidity in the lung can result in the hygroscopic growth of susceptible aerosol particles or droplets. The term hygroscopic growth describes the increase in particle diameter which occurs as the result of association with water vapor. The influence of hygroscopicity upon lung deposition of aerosols has been a productive area of research in industrial hygiene, environmental sciences, and inhalation toxicology. Many pharmaceutical inhalation aerosols display hygroscopic behavior in their passage through the airways; however, the effect has been neglected. Controlling the phenomenon of hygroscopic growth and, thus, the related lung deposition of aerosols might result in the therapeutic advantage of targeting the site of action. Such an approach might also allow identification of the location of pharmacologic receptor sites in the lung. This Review discusses an approach to achieving control of hygroscopic growth of aerosol particles. Theoretical and experimental studies have indicated that inhaled particle diameters increased significantly for drugs commonly administered to the lung. The presence of certain additives, notably glycerol, cetyl alcohol, and lauric and capric acids, has been demonstrated to reduce the growth of particles under conditions approaching those in the lung. Very few quantitative studies of the nature discussed herein have appeared in the literature. It is conceivable that an aerosol particle could be fabricated of known initial size and density, and by implication, deposition characteristics, and this might be induced to follow specific growth kinetics to enhance deposition in a particular region of the lung. Thus, physical targeting of regions within the lung might be achieved.     

Guidance in the Setting of Drug Particle Size Specifications to Minimize Variability in Absorption

Purpose. To provide guidance in setting particle size specifications for poorly soluble drugs to minimize variability in absorption. Methods. A previously reported computer method was used to simulate the percent of dose absorbed as a function of solubility, absorption rate constant, dose, and particle size. Results. The simulated percent of dose absorbed was tabulated over a realistic range of solubilities, absorption rate constants, and doses using drug particle sizes that might be typically found in a dosage form. Conclusions. The greatest effect of particle size on absorption was simulated for low dose- low solubility drugs. In general, the sensitivity of absorption to particle size decreased with increasing dose or solubility. At a solubility of 1 mg/mL, particle size had practically no effect on the percent of dose absorbed over the range of doses simulated (1–250 mg).     

Microencapsulation of blackberry pulp with arrowroot starch and gum arabic mixture by spray drying

Abstract

This research work aimed to obtain blackberry pulp powder by spray drying and, by an experimental design, evaluated the effect of inlet air temperature (100–150?°C) and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2 on the physicochemical properties of the powders. Arrowroot starch and gum arabic present glass transition temperature (Tg) values above 100?°C; hence it was possible to employ them as carriers in blackberry pulp spray drying in order to increase Tg of the system. Powder yield and solubility increased with increasing blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2, whereas hygroscopicity decreased. Yield, solubility and hygroscopicity of the powders increased and water activity decreased, with increasing inlet air temperature. The powders presented low moisture content and water activity. Temperature of 143?°C and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:1.78 were the optimal conditions to obtain high yield and blackberry powders that are soluble in water and less hygroscopic.     

Advances in lipid-based drug delivery: enhancing efficiency for hydrophobic drugs

Introduction: Many drug candidates with high therapeutic efficacy have low water solubility, which limits the administration and transport across physiological barriers, for example, the tumor tissue barrier. Therefore, strategies are needed to permeabilize the physiological barriers safely so that hydrophobic drugs may be delivered efficiently.

Areas covered: This review focuses on prospects for therapeutic application of lipid-based drug delivery carriers that increase hydrophobic drugs to improve their solubility, bioavailability, drug release, targeting and absorption. Moreover, novel techniques to prepare for lipid-based drug delivery to extend pharmaceuticals with poor bioavailability such as surface modifications of lipid-based drug delivery are presented. Industrial developments of several drug candidates employing these strategies are discussed, as well as applications and clinical trials.

Expert opinion: Overall, hydrophobic drugs can be encapsulated in the lipid-based drug delivery systems, represent a relatively safe and promising strategy to extend drug retention, lengthen the lifetime in the circulation, and allow active targeting to specific tissues and controllable drug release in the desirable sites. However, there are still noticeable gaps that need to be filled before the theoretical advantage of these formulations may truly be realized such as investigation on the use of lipid-based drug delivery for administration routes. This research may provide further interest within the area of lipid-based systems, both in industry and in the clinic.     

Effects of Highly Hygroscopic Excipients on the Hydrolysis of Simvastatin in Tablet at High Relative Humidity

Effects of highly hygroscopic sorbitol, citric acid, sodium carboxymethyl cellulose or polyvinylpolypyrrolidone, on the hydrolysis of simvastatin in tablets at 25°/90% RH were studied. The simvastatin tablets were prepared by direct powder compression. Simvastatin and its hydrolyte, simvastatin acid, were quantitatively analysed by high performance liquid chromotography. The hygroscopicity, water swelling ratio, water solubility and pH of the four hygroscopic excipients were investigated. During the investigation period, the weight gain of sorbitol or citric acid increased faster than that of polyvinylpolypyrrolidone or sodium carboxymethyl cellulose at 25°/90% RH, accordingly, the moisture sorption of the tablets containing citric acid or sorbitol (T-3 or T-6) were more than that of the tablets containing sodium carboxymethyl cellulose or polyvinylpolypyrrolidone (T-4 or T-5). The increase of simvastatin acid content with time at 25°/90% RH for the tablets was in the following order: T-6 < T-4 < T-3 < T-5. The effects of the four excipients on the hydrolysis of simvastatin in tablet were related to not only their hygroscopicity but also their other properties, such as moisture retention capacity and pH. Sorbitol as hygroscopic excipient in tablet can most effectively prevent the hydrolysis of simvastatin in tablet.     

甲钴胺的引湿性探讨

目的：了解甲钴胺的引湿特性,探讨化学对照品使用和贮存中应注意的问题。方法：采用动态水分吸附分析技术（DVS）研究甲钴胺在不同湿度条件下吸收水分的趋势和程度,以容量滴定法测定其水分的均匀性。结果：甲钴胺具有引湿性,且在一定湿度条件下吸水后仍具有较强的引湿性。结论：本研究为确定甲钴胺适宜的分装条件、包装用瓶和使用方式等提供了数据支持和参考依据。     

Preparation and Characterization of Tablet Formulation based on Solid Dispersion of Glimepiride and Poly(ester amide) Hyperbranched Polymer

The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride and poly(ester amide) hyperbranched polymer into a tablet using a direct-compression tabletting technique was investigated. Tablet cores were additionally coated with hydroxypropyl methylcellulose phthalate in order to protect the extremely hygroscopic solid dispersion from atmospheric moisture. Preliminary stability studies show that glimepiride, which is in amorphous form within solid dispersion, is chemically stable, even if tablets are exposed to elevated temperature and/or moisture. In-vitro dissolution studies show some impact of storage conditions on the tablet cores disintegration time and, consequently, drug release rate. Glimepiride solubility also deteriorates somewhat, most probably due to its partial recrystallization. Storage conditions much less affect the physical stability of coated tablets, which was ascribed to reduced tablet hygroscopicity due to the presence of protecting coating. The hyperbranched polymers are rather new and complex macromolecules. Therefore, we addressed also the biocompatibility of hyperbranched polymer, i.e., its impact on haemolysis of the red blood cells. The concentration required for the haemolytic effect on the red blood cells is around 100-times higher than its expected gastrointestinal luminal concentration, which makes the occurrence of hyperbranched polymer mediated cytotoxicity very unlikely.     

复方山楂散的质量标准研究

目的：建立复方山楂散的质量控制方法，提供分装车间的相对湿度要求。方法：采用TLC对山楂、决明子进行定性鉴别：中和法测定总有机酸舍量[以枸檬酸(C6H8O7)计]；并测定药粉的吸湿平衡曲线。结果：定性鉴别方法专属性强，舍量测定结果准确，平均回收率为100．34％，RSD为0．46％。药粉暴露于相对湿度大于54％的环境中吸湿率迅速增大。结论：本法简便、准确，可有效地控剥复方山楂散的质量；分装车间的相对湿度应控制在54％以下。