Evaluation of the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems III: anti-allergic effects of hot water extracts on IgE-mediated immediate hypersensitivity in mice

To evaluate the safety and efficacy of Glycyrrhiza uralensis root extracts produced using artificial hydroponic and artificial hydroponic-field hybrid cultivation systems, we investigated anti-allergic action in mice using IgE-mediated immediate hypersensitivity. Hot water extracts obtained from the roots of Glycyrrhiza uralensis cultivated using two systems were orally administered at a dose of 100 mg/kg as glycyrrhizin (GL) and compared with the commercial crude drug, Glycyrrhizae Radix. Both the artificial hydroponic and artificial hydroponic-field hybrid cultivated root extracts showed anti-allergic effects on IgE-mediated immediate hypersensitivity in mice, as did the commercial crude drugs. These results highlight the potential for artificially cultivated roots of Glycyrrhiza uralensis to be used as an alternative medicinal source.     

中药治疗过敏性鼻炎作用机制的研究进展

过敏性鼻炎是一种常见的呼吸系统疾病,属祖国医学的“鼻鼽”范畴。其发病率在全球范围内有逐年上升的趋势,过敏性鼻炎的防治和新药的研究已在世界范围内受到广泛的关注。近几年中医药在防治过敏性鼻炎研究进展较快,对其防治机制在细胞水平、分子水平和基因水平进行了大量深入研究,根据中药作用机制的不同,对近年来中药治疗过敏性鼻炎的实验研究进行综述,为从传统中药中挖掘新药提供思路。     

Development and evaluation of an artificial membrane for determination of drug availability

Various artificial membranes (e.g. PAMPA) and cellular-based membranes (e.g. Caco-2) are used for screening during early stages of drug discovery. However, these methods are not well suited for evaluation of pharmaceutical formulations and the effects of various excipients on drug availability. When drug molecules permeate biological membranes they encounter two types of permeation resistance, a membrane resistance in the lipophilic membrane and diffusion resistance in the unstirred water layers adjacent to both surfaces of the lipophilic membrane. We have developed an artificial membrane that is cheap and simple to prepare. The unstirred water layer consists of a hydrated semi-permeable cellophane membrane with a molecular weight cutoff (MWCO) of 12,000-14,000 Da and a lipophilic membrane of pure n-octanol in a nitrocellulose matrix. In the diffusion cell the hydrated cellophane membrane (thickness 210-230 microm) is on the donor side and the lipophilic octanol membrane (thickness about 120 microm) on the receptor side. Permeation of ionizable lipophilic drug molecules was diffusion-controlled when the drug was unionized but lipophilic membrane controlled when the drug was ionized. Drug permeation patterns from cyclodextrin containing formulations through the membrane were similar to those previously observed for biological membranes such as hairless mouse skin and the eye cornea.     

抗变态反应药物富马酸卢帕他定的药理及临床评价

富马酸卢帕他定是一种长效血小板活化因子受体及H1受体双重拮抗剂,它通过特异性阻断上述受体而抑制过敏反应,于2003年3月首次在西班牙上市,目前已广泛用于治疗过敏性鼻炎和慢性荨麻疹等过敏性疾病,获得良好的临床疗效。文中就其药理作用、药动学及其临床研究等作一综述。     

HPLC指纹图谱法研究峨眉黄连与三角叶黄连

目的建立三角叶黄连Coptis deltoidea和峨眉黄连Coptis omeinsis的根茎、根、叶的高效液相指纹图谱。方法采用HPLC-DAD法测定峨眉黄连、三角叶黄连及黄连的根茎、根和叶中小檗碱的含量及各部位的指纹图谱,用指纹图谱相似度评价方法综合比较黄连药材的差异。结果从化学组分及各组分含量的相似度综合比较,同一分布区域内的3种黄连中,峨眉黄连与三角叶黄连更相似,同为雅连使用有一定的依据。结论所用方法简便、重复性好,可用于黄连属植物的化学组分与种间鉴别的比较依据。     

Treatment of experimental poisoning produced by extracts of Amanita phalloides.

Agents known to antagonize in mice the lethal effects of phalloidin or α-amanitin, two major toxins of the deathcap, Amanita phalloides, were tested against lethal doses of the whole extract from the mushroom. The extract was given in fractionated doses that produced death in a temporal pattern similar to the one seen clinically or after α-amanitin. No activity against the extract was provided by drugs with prophylactic properties against phalloidin such as rifampicin and phenylbutazone. Cytochrome c, an agent with curative properties against α-amanitin, was also ineffective. However, prednisolone and silymarin as antidotes increased markedly the survival after the extract. Similarly, only these two agents protected mice against poisoning by α-amanitin. The efficacy of prednisolone and silymarin against the extract may thus be due to their capacity to prevent the toxicity of amatoxins. The latter are thought to be responsible for the fatalities in clinical intoxications, and they are presumed to be continuously reabsorbed because of enterohepatic recirculation. It is suggested that the fatalities after single lethal doses of the mushroom extract were caused predominantly by phallotoxins, whereas with fractionated administration of the extract, the fatalities may be due mainly to amatoxic effects.     

Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens

Oral administration of the perilla leaf extract (PLE) to mice inhibits inflammation, allergic response, and tumor necrosis factor-alpha production. We also found that PLE suppressed the tumor necrosis factor-alpha (TNF-alpha) production in vitro. Using the inhibitory activity of TNF-alpha production in vitro as the index for isolation, we searched the active constituents from PLE and isolated luteolin, rosmarinic acid and caffeic acid as active components. Among the isolated compounds, only luteolin showed in vivo activity: inhibition of serum tumor necrosis factor-alpha production, inhibition of arachidonic acid-induced ear edema, inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ear edema and inhibition of oxazolone-induced allergic edema. These results suggest that luteolin is a genuinely active constituent which is accountable for the oral effects of perilla.     

儿童药品临床综合评价方法研究——以儿童抗过敏药物为例

目的 为我国儿童药品临床综合评价工作的全面开展提供借鉴.方法 以儿童抗过敏药物为例,从主题遴选、评价内容与维度、评价指标、评价方法及评价结果报告等环节探索医疗机构开展儿童药品临床综合评价的方法.结果 与结论在开展儿童药品临床综合评价时,可在国家临床综合评价相关指南指导下,按照重要性、相关性以及可评估性三大原则遴选评价主...     

不同厂家黄连配方颗粒中盐酸小檗碱、盐酸巴马亭和盐酸药根碱含量比较

目的　考察不同厂家黄连配方颗粒中盐酸小檗碱、盐酸巴马亭和盐酸药根碱含量。方法　用高效液相色谱法测定盐酸小檗碱、盐酸巴马亭和盐酸药根碱含量。色谱柱为Diamonsil C18 (4 6 mm×250 mm, 5μm); 流动相为0 2 mol·L-1磷酸二氢钠(用磷酸调节pH至3 0) 乙腈(70∶30); 流速为1 mL·min-1; 柱温为30 ℃; 检测波长为345 nm。结果　不同厂家黄连配方颗粒中盐酸小檗碱含量为3 .67~72. 53 mg·包-1, 盐酸巴马亭含量为0 .60~28. 70 mg·包-1, 盐酸药根碱含量为5. 40~26 .54 mg·包-1。结论　不同厂家产品盐酸小檗碱、盐酸巴马亭和盐酸药根碱含量差异显著。     

植物内生菌生物活性物质研究新进展

以往 ,抗生素的主要来源是土壤微生物 ;而今 ,植物内生菌这一多样性十分丰富却尚未开发的微生物类群看来是一巨大资源。植物内生菌是生活于植物组织间隙的微生物 (主要是真菌和细菌 )。其中一些内生菌可能会产生在微生物 -宿主关系中发挥作用的生理活性物质 (如 :抗细菌 ,抗真菌 ,抗病毒物质等 )。鉴于这些次级代谢产物在自然界中所起的重要作用 ,对于它们在医药 ,农业 ,工业领域的应用越来越受到人们的关注。全球范围分离植物内生菌及其天然产物的工作正在展开。本文主要概述了植物内生菌及其生理活性物质研究的最新进展 ,希望以此使人们更好的认识到它们对于人类的重要性及价值。     

Automatic multicommmutated flow system for diffusion studies of pharmaceuticals through artificial enteric membrane.

An automatic flow procedure with spectrophotometric detection was developed for the study of pharmaceuticals diffusion through an artificial enteric membrane. The manifold comprised two independent flow pathways, gathered by a diffusion unit with two compartments and an enteric lipophilic membrane. The pathways were automatically filled with solutions simulating digestive and plasmatic conditions by means of four solenoid valves. The diffusion of pharmaceuticals from the enteric to the plasmatic compartment was performed in closed loop pathways, and was continuously monitored by a flow cell coupled to the acceptor solution pathway. The volumes of the digestive and plasmatic solutions were 6.0 and 3.6 ml, respectively, which comprised filling unit compartment, pumping tubing and connecting flow lines. Pumping flow rates of donor and acceptor solutions were maintained at 6.0 and 2.5 ml min(-1), respectively. The proposed system was employed in diffusion studies of caffeine and aminophylline, and in the evaluation of the influence of tensioactive agents on the diffusion process. After continuous solutions circulation for 60 min, caffeine concentration in the acceptor stream was ca. 18% of its initial concentration at the digestive compartment. The system could be programmed to perform several replicates, stopping them with different degrees of diffusion without operator assistance. The data generated by the spectrophotometer was read by the microcomputer as a time function, and stored for further mathematical treatment.     

Preparation and in vitro evaluation of silk fibroin microspheres produced by a novel ultra-fine particle processing system

The objective of this study was to prepare silk fibroin SF microspheres containing the enhanced green fluorescent protein (EGFP) by using a novel ultra-fine particle processing system (UPPS) and to evaluate the microspheres as possible carriers for long-term delivery of sensitive biologicals. The drug content, encapsulation efficiency, and in vitro release were evaluated by Microplate Absorbance Reader. The particle size distribution and morphology of the microspheres were analyzed by Malvern Master Sizer 2000 and scanning electron microscopy. The distribution of EGFP and the interactions between SF and EGFP were investigated by Confocal Laser Scanning Microscopy, FTIP, Raman and NMR spectroscopy. The results showed that spherical microspheres with narrow size distribution, glossy and dense surface were successfully manufactured by using UPPS technology and over 95% of EGFP encapsulation efficiency and uniform drug distribution in the microspheres were achieved. Furthermore, a burst free and sustained release of encapsulated EGFP for a period of 50 days in deionized water was obtained. In conclusion, the novel UPPS technology could be used to manufacture SF matrix microspheres as a potential long-term protein delivery system to improve patient compliance and convenience.     

Development of a novel model for comparative evaluation of intranasal pharmacokinetics and effects of anti-allergic nasal sprays

For locally acting drugs, an extended residence time in the nasal cavity is desirable and related to a prolonged effect. We sought to develop a model for comparative determination of intranasal pharmacokinetics. We embedded human respiratory tissue into a solid matrix and coated the surface with artificial nasal fluid. Nasal spray suspensions of fluticasone propionate (FP) and budesonide (Bud) as well as a solution of azelastine hydrochloride (AZ) were applied onto the surface and removed after 30 min to simulate mucociliary clearance. As exemplary anti-inflammatory measure, we evaluated the inhibition of IL-8 release from epithelial cells. FP and Bud were initially bound to the same extent to the tissue gel while AZ displayed a more 4-fold higher binding than FP or Bud. After equilibrium with plasma, approximately 5-fold higher tissue concentrations of AZ compared to FP and 77-fold higher levels in relation to Bud were determined. This tissue retention revealed an excellent correlation with the volume of distribution of the respective drugs (r = 0.9999, p ? 0.05). The inhibitory effect of FP on IL-8 release was approximately 5-fold more pronounced compared to AZ. The present model realistically mirrors conditions in vivo where solubility and tissue absorption of intranasally applied drugs compete with mucociliary clearance mechanisms.     

Total analysis system for tumor promoter microcystins produced by cyanobacteria

Microcystins, produced by freshwater cyanobacteria, are cyclic peptide hepatotoxins and tumor promoters. An outbreak of human poisoning attributed to microcystins has been reported in Caruaru, Brazil in 1996, where exposure through renal dialysis led to the death of 50 patients. Although such severe acute effects on human health seem to be rare, microcystins poses problems to human health which could result from low-level, chronic exposure to microcystins in drinking water. It is therefore important to monitor the levels of microcystins in water reservoirs where cyanobacterial blooms occur. We have developed a total analysis system for microcystins using GC-MS and LC-MS. This comprises initial screening of samples to check for the presence of microcystins by detecting 2-methyl-3-methoxy-4-phenylbutyric acid as an ozonolysis product using thermospray interface LC-MS and electron ionization/GC-MS. If a sample is positive in a screening test, it will be necessary to follow through with identification and quantification. Frit-FAB interface LC-MS allowed the rapid identification of microcystins in cyanobacteria and lake water, and also enabled us to identify microcystins and their metabolites formed in vivo in mouse liver. Finally, Frit-FAB/LC-MS using selected ion monitoring could be used for quantitative analysis of microcystins in lake water in the low nanogram range. The total analysis system proposed in the present study should be applicable to studies of the metabolism of microcystins, of their detoxification, and those of the mechanism(s) of the accumulation in the food chain.     

Pharmacology and clinical efficacy of desloratadine as an anti-allergic and anti-inflammatory drug

Desloratadine is a biologically active metabolite of the second-generation antihistamine loratadine. Desloratadine is a highly selective peripheral H₁ receptor antagonist that is significantly more potent than loratadine. Results of in vitro and in vivo studies have suggested that desloratadine has anti-allergic effects that are unrelated to its ability to antagonise the effects of histamine. Desloratadine inhibits the expression of cell adhesion molecules, inhibits the generation and release of inflammatory mediators and cytokines, attenuates eosinophil chemotaxis, adhesion and superoxide generation. Studies in animals indicate that desloratadine does not cross the blood-brain barrier and therefore does not cause sedation and does not impair cognition or psychomotor performance. Desloratadine has an excellent overall safety profile. It has no effect on QRS and QT_c intervals and does not cause arrhythmias. Desloratadine is not associated with any significant changes in gastrointestinal function. In clinical studies, oral desloratadine is rapidly absorbed and bioavailability is not affected by ingestion with food or grapefruit juice. The half-life of desloratadine in humans is 27 h; the linear kinetic profile is unaltered by race or gender. Desloratadine is not a substrate for P-glycoprotein or organic anion transport polypeptide and the drug does not appear to be metabolised to a significant extent by the cytochrome P450 CYP3A4 pathway. It therefore may be safely administered with ketoconazole, erythromycin, fluoxetine, or azithromycin. Clinically, desloratadine effectively controls both nasal and non-nasal symptoms of seasonal allergic rhinitis (SAR), including nasal congestion. Desloratadine also provides significant relief of SAR symptoms in patients with co-existing asthma and is effective in the treatment of chronic idiopathic urticaria. Desloratadine improves quality of life and is well-tolerated.     

动物活体自动采样技术的应用和评价

介绍在动物实验中一种先进的生物样品自动采集与处理系统,该系统结合液相色谱/质谱/质谱(LC/MS/MS)分析方法,可以为临床前药动学研究、药效学研究和安全性评价提供可靠的实验数据。利用该系统能够在清醒的、自由活动的实验大鼠、小鼠等啮齿类动物及灵长类动物完成生物样品的定时自动采集,并进行即时处理。不但节约人力,且大大提高了对少量低浓度生物样品的实验数据准确性;与此同时,还能实时监测实验动物的其他生理参数,从而可减少所用动物数量,改善动物的舒适性。若能把自动生物样品采集技术和现代先进的LC/MS/MS分析方法合并使用,则可显著提高临床前研究的速度和质量,以满足高通量药物筛选的要求。自动采样系统被我们用于大鼠口服卡马西平的药动学实验,结果证实它确实是临床前药动学、药效学研究及安全性评价的有效工具。     

Combinative method using HPLC fingerprint and quantitative analyses for quality consistency evaluation of an herbal medicinal preparation produced by different manufacturers

A combinative method using HPLC-DAD fingerprint and quantitative analysis was developed and validated for manufacturer-to-manufacturer quality consistency evaluation of Yiqing preparations. For fingerprint analysis, 22 peaks were selected as the characteristic peaks to evaluate the similarities of different samples collected from different manufacturers. The similarities of 12 Yiqing samples were beyond 0.90, indicating that samples from different manufacturers were, to some extent, consistent. Additionally, simultaneous quantification of nine markers including berberine, aloe-emodin, rhein, emodin, chrysophanol, baicalin, baicalein, wogonoside, and wogonin in Yiqing was performed to interpret the quality consistency. The results from the quantitative data showed that the contents of these nine marker compounds were quite consistent for batches produced within one manufacturer and significantly different from manufacturer-to-manufacturer. This study demonstrated that a combination of the chromatographic fingerprint and quantitative analysis offers an efficient way to quality consistency evaluation of herbal preparation.