An Artificial Gut/Absorption Simulator: Simultaneous Evaluation of Desupersaturation and Absorption from Ketoconazole Supersaturated Solutions

For supersaturating formulations of BCS-II compounds, which by definition have high intestinal permeability, a closed USP apparatus does not provide the necessary absorptive conditions during dissolution. To address this, an artificial gut simulator (AGS) has been constructed consisting of a 2.5 mL donor compartment in which a hollow fiber-based absorption module is suspended. Drug from donor diffuses across the hollow fiber membrane to be absorbed by the continuously flowing intraluminal receiver fluid. The membrane surface area and intraluminal fluid flow rate are tuned to obtain the physiologically observed absorption rate constant for a weakly basic, poorly water-soluble model compound, ketoconazole (KTZ). Supersaturated solutions of KTZ were generated in the donor in pH 6.5 phosphate buffer by the pH-shift method in the absence (closed system, control) and presence (open system, biorelevant) of an optimally or suboptimally tuned absorption module. Drug concentrations in the donor and intraluminal fluids were determined by in-line UV spectroscopy. The presence of an absorptive sink reduced the supersaturated solution's crystallization propensity, more so in the case of the optimally tuned AGS. This study demonstrates the significance of simulating absorption of drug at a physiological rate during dissolution studies, especially to predict the performance of formulations of BCS-II drugs.     

Toxicological evaluation of Yulangsan polysaccharide in Wistar rats: A 26-week oral gavage study

Although numerous studies have proven the medicinal values of Yulangsan polysaccharide (YLSP), the toxicity of this active ingredient is unknown. In the acute toxicity study, a single oral administration of 24 g/kg YLSP caused neither toxicological symptoms nor mortality, and the LD₅₀ was estimated >24 g/kg. In the chronic toxicity study, we administered doses of 0, 0.6, 1.2 and 2.4 g/kg YLSP in rats by oral gavage for 26 weeks followed by a 3-week recovery period. There was no mortality or remarkable clinical signs observed during this 26-week study. Additionally, there were no toxic differences in the following parameters: body weight, food consumption, hematology, clinical biochemistry, organ weight, and macroscopic findings. There were no adverse effects on histopathology observed in males or female rats treated with YLSP. Based on the results, the no-observed-adverse-effect-level of YLSP in rats is greater than 2.4 g/kg when administered orally for 26 consecutive weeks.     

岗梅全长转录组测序及其三萜皂苷生物合成相关基因的挖掘

目的:获得岗梅全长转录组数据库,为深入挖掘岗梅功能基因奠定基础。方法:采用基于PacBio Sequel平台的单分子实时测序技术获取岗梅的根、茎、叶样品的转录组数据,并利用非冗余蛋白(NR)、核苷酸序列(NT)、SwissProt蛋白序列数据库、京都基因与基因组百科全书(KEGG)、真核生物相邻类的聚簇(KOG)、蛋白家族(Pfam)、基因本体(GO)进行注释,分析并鉴定编码三萜皂苷生物合成的关键酶的转录本。结果:全长转录组共获得89629个转录本,其中81313个在公共数据库进行了注释。KEEG代谢通路富集分析表明,623个转录本参与岗梅中三萜皂苷合成相关的3条代谢通路,其中263个转录本编码了三萜皂苷生物合成途径的21个关键酶。此外,还预测了2471个转录因子、40421个简单重复序列位点、22119个长链非编码RNA(lncRNA)和29131个mRNA。结论:丰富了岗梅的转录组数据,并为鉴定参与三萜皂苷和其他次生代谢物生物合成的候选基因提供参考,促进其分子生物学和基因组学的研究。     

非靶向代谢组学揭示天葵不同部位差异代谢物及其主要代谢途径

目的:利用非靶向代谢组学挖掘天葵非药用部位潜在的药用价值。方法:以天葵茎、叶、花为材料,利用超高效液相色谱-质谱法对其进行非靶向代谢组学分析。结果:天葵茎、叶、花中共鉴定出16大类101个差异代谢物(DAMs),其中包含羧酸及其衍生物、有机含氧化合物、脂质、苯及其取代衍生物、生物碱、黄酮类、萜类、苯丙素类、酚酸类、核苷酸、有机盐、内酯、有机酸、内源性植物激素、氨基酸和13个其他物质。通过聚类和京都基因与基因组百科全书(KEGG)分析发现,天葵不同部位的DAMs代谢模式存在一定的差异;其主要代谢途径为苯丙氨酸代谢途径、ABC转运途径、氨酰-tRNA合成途径及苯丙氨酸、酪氨酸和色氨酸生物合成途径。结论:通过天葵不同部位间DAMs的鉴定及其生物合成途径的分析,确定天葵茎、叶、花富含多种具有药用功效的代谢活性物质,可为天葵茎、叶、花的资源开发利用提供参考。     

基于“药辅合一”理念的Pickering乳技术提升儿科用药羚珠散中石菖蒲挥发油热稳定性的研究

目的 在“药辅合一”理念下导入Pickering乳技术,提升儿科用药羚珠散中石菖蒲挥发油的稳定性。方法 对羚珠散各饮片粉末进行初步表征,确定稳定剂。通过成乳量、包油量和乳剂形态筛选出最佳稳定剂质量浓度、油水比和制备方法。并使用近红外光谱（nearinfraredspectroscopy,NIRS）分析石菖蒲油在Pickering乳中的包裹状态。比较不同时间下各组别挥发油的保有量、丙二醛和过氧化物的含量。再通过GC-MS分析其中成分的变化趋势。结果 筛选出珍珠粉作为Pickering乳的稳定剂,珍珠粉质量浓度为65 mg/mL,油水比9∶11为最优成乳条件,高压均质法为最优的制备方法,NIRS分析可知石菖蒲挥发油被珍珠粉包裹,Pickering乳液中没有形成新的化学键。对比各组在不同时间段下石菖蒲油的保有率和其中丙二醛和过氧化物含量,可知40℃放置1、3、8 h的Pickering乳剂相比于石菖蒲挥发油组有更高的保有率和更低的氧化程度。GC-MS分析结果表明,相比于石菖蒲挥发油组,Pickering乳组挥发性成分的稳定性显著提高。结论 在“药辅合一”理念下Pickering乳可用于含油固...     

丹参多酚酸提取物中异紫草酸的结构确定

目的 确定从丹参多酚酸提取物中分离得到的1个紫草酸同分异构体(异紫草酸)的结构。方法 利用质谱、核磁共振、化学转化以及ECD等方法确定其化学结构。结果 该化合物鉴定为[(2S,3S)-4-(2-羧基乙烯基)-2-(3,4-二羟基苯基)-2,3-2H-7-羟基-3-苯骈呋喃羧酸-3-[(1R)-1-羧基-2-(3,4-二羟基)乙基]酯](异紫草酸)。结论 总结了紫草酸同分异构体核磁数据的规律,进一步明确了异紫草酸的平面结构并首次确定了异紫草酸的立体结构。     

五味子中1个新的联苯环辛烯类木脂素

目的 研究中药五味子Schisandra chinensis的木脂素类化学成分。方法 采用硅胶柱色谱、中压反相柱色谱、半制备和制备液相对五味子中富含木脂素类成分的石油醚萃取部位进行分离、纯化,通过波谱数据鉴定化合物的结构。结果 从五味子中分离得到了26个化合物,分别鉴定为绿叶五味子素B(1)、sphaerandrin A(2)、sieverlignan E(3)、arisanschinin G(4)、widdaranalF(5)、戈米辛A(6)、戈米辛B(7)、戈米辛D(8)、戈米辛G(9)、(-)-戈米辛K1(10)、(+)-戈米辛K2(11)、(-)-戈米辛L₁(12)、(+)-戈米辛M1(13)、戈米辛N(14)、当归酰戈米辛H(15)、当归酰戈米辛O(16)、当归酰戈米辛Q(17)、苯甲酰戈米辛Q(18)、五味子醇甲(19)、五味子甲素(20)、五味子乙素(21)、五味子丙素(22)、五味子酯丙(23)、neglschisandrin E(24)、7(18)-dehydroschisandro A(25)、安五脂素(26),其中24个为联苯环辛烯类木脂素(...     

黑布药膏的化学成分表征研究

黑布药膏系常用的院内制剂,由五倍子、蜈蚣等制成,临床疗效确切,但其药效物质基础尚未全面阐明。本研究采用超高效液相色谱-高分辨飞行时间质谱联用技术（UPLC-Q-TOF-MS/MS）对黑布药膏及其生药混合物的化学成分进行定性分析,并探讨了制剂前后成分的差异。在电喷雾（ESI）正、负离子模式下,根据精确相对分子质量、特征碎片离子、色谱保留时间等初步鉴定出73个化合物,其中生药混合物、黑布药膏分别鉴定了57、65个化合物,包括鞣质类、酚酸类、核苷类、氨基酸类等,在制备过程中,化学结构发生变化的成分主要集中在鞣质类。结果表明,UPLC-Q-TOF-MS/MS技术可以灵敏、高效地表征黑布药膏制剂中所含的化学成分及其在制剂过程中的结构变化,为充分阐明黑布药膏药效物质基础和制剂工艺的合理性及后续制剂质量标准提升研究提供重要依据。     

泻白散及其主药体外抗氧化活性研究

目的 建立泻白散和方中3味主药甘草、地骨皮、桑白皮的体外抗氧化活性测定方法,并对31批药材和10批泻白散煎液的抗氧化活性进行测定。方法 采用紫外可见分光光度法检测一定浓度的药材提取液引起DPPH溶液吸光度（A）值降低,考察波长为517 nm,分别探索3味药材抗氧化活性成分的提取条件;并进行不同溶剂的吸收考察、专属性考察、DPPH线性考察、药材提取液线性考察、精密度试验、重复性试验、耐用性考察等方法学验证;以清除DPPH自由基的半抑制浓度（IC₅₀）作为评价指标,对泻白散和方中3味药材的体外抗氧化活性进行考察。结果 地骨皮、甘草、桑白皮和泻白散提取液的IC₅₀均值为0.31、1.24、1.49和0.91 g/L,泻白散提取工艺对方中药物抗氧化活性的保留均值为56%。结论 建立的抗氧化活性测定方法可用于泻白散及方中主药的抗氧化活性测定,为多维度评价中药和中药材质量提供新思路。     

The structural composition of components contributes to the superiority of the geoherb Alisma orientale for “diuresis and diffusing dampness”

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale. The effects of “diuresis and diffusing dampness” using salt-made Alisma orientale from seven different origins were investigated through pharmacodynamic experiments in vivo and in vitro. The results indicated that salt-made Alisma orientale from different origins had diuretic efficacy; this was demonstrated by the significant increase in the volume of rat urine, the concentration of Na⁺, K⁺, and Cl⁻ in the urine, and the significant decrease in the levels of AQP-2 in rat renal medulla and HK-2 cells. It was also revealed that the diuretic effect of salt-made Alisma orientale from Fujian Province is stronger than those from other provinces. Moreover, the main components and their proportions in the salt-made Alisma orientale samples were further analyzed via principal component analysis. The results showed that alisol A 24-acetate, alisol B, and 23-acetyl alisol B are the main components of salt-made Alisma orientale, and the optimal structural ratio of alisol A 24-acetate, alisol B, and 23-acetyl alisol B was found to be 5.38 : 14.34 : 11.31 via optimizing the ratios of the three main components. It is worth noting that the optimal ratio of the three main components after optimization is the closest to the ratio of the three main components in salt-made Alisma orientale from Fujian Province. This paper reveals the “mystery” of the content ratio of the main active components and its effect on the efficacy, and showed that the proportional relationship between the content of multiple components is the key to their interactions. Therefore, this method of evaluating the quality of salt-made Alisma orientale is obviously reliable, and this study lays the foundations for quality evaluation of salt-made Alisma orientale and other herb slices.

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale.