用日本ＯＬＹＭＰＵＳ Ｓ－４５０型扫描电子显微镜对２５枚天然牛黄的表面、剖面和核心，以及１６枚牛体培育牛黄的表面和剖面进行了５００￣１０００倍连续扫描观察，发现天然牛 黄的层次结构比牛体培育牛黄的层次多而且明显；两种牛黄均具有梅花状、蜂巢状、珊瑚石状和树根状的结构特征，与人的胆红素型结石十分类似。在天然牛黄的核 心均未见到异物。

正 天然牛黄(natural ox gallstone)为牛的胆结石,由于产量极少,供求困难,国内于1956年参照天然牛黄的主要成分制成人工牛黄(artificial ox gallstone),作为天然牛黄的代用品。从1974年以来,很多省区如吉林、广东、内蒙古等都先后进行了人工培育牛黄的试验,并试验成功培育牛黄(cultured ox gallstone)。其方法是用手术在牛胆囊内植入异物为核,促使胆汁成分的沉积与结石的形成,经过一段时间后,将异物取出,上面的沉积物即为培育牛黄。本文目的是探讨天然牛黄与培育牛黄的结构特征。

本文利用云南中医学院“中国药用动物医药数据库”进行检索共检出４３年牛黄文献（１９４９－１９９２年）６６２篇，对牛黄所在基原、产地、化学成分、药理（对中枢神经系统、心血管系统、造血系统、内分泌系统、免疫系统和利胆、抗炎、抗肿瘤及对平滑肌的作用）、资源（天然牛黄、合成牛黄、人工培植牛黄、体外合成牛黄和代用品）、鉴别（物理、化学、薄层和显微鉴别）和其它方面进行了动态研究，并综述全文。

体外培育牛黄可作为天然牛黄的理想替代品,该文就其主要化学成分及其分析、药理活性、临床应用以及相关制剂及其分析等方面的最新研究进展加以综述.

Animal biles and gallstones are popularly used in traditional Chinese medicines, and bile acids are their major bioactive constituents. Some of these medicines, like cow-bezoar, are very expensive, and may be adulterated or even replaced by less expensive but similar species. Due to poor ultraviolet absorbance and structural similarity of bile acids, effective technology for species differentiation and quality control of bile-based Chinese medicines is still lacking. In this study, a rapid and reliable method was established for the simultaneous qualitative and quantitative analysis of 18 bile acids, including 6 free steroids (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, hyodeoxycholic acid, and ursodeoxycholic acid) and their corresponding glycine conjugates and taurine conjugates, by using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This method was used to analyze six bile-based Chinese medicines: bear bile, cattle bile, pig bile, snake bile, cow-bezoar, and artificial cow-bezoar. Samples were separated on an Atlantis dC(18) column and were eluted with methanol-acetonitrile-water containing ammonium acetate. The mass spectrometer was monitored in the negative electrospray ionization mode. Total ion currents of the samples were compared for species differentiation, and the contents of bile acids were determined by monitoring specific ion pairs in a selected reaction monitoring program. All 18 bile acids showed good linearity (r(2) > 0.993) in a wide dynamic range of up to 2000-fold, using dehydrocholic acid as the internal standard. Different animal biles could be explicitly distinguished by their major characteristic bile acids: tauroursodeoxycholic acid and taurochenodeoxycholic acid for bear bile, glycocholic acid. cholic acid and taurocholic acid for cattle bile, glycohyodeoxycholic acid and glycochenodeoxycholic acid for pig bile, and taurocholic acid for snake bile. Furthermore, cattle bile, cow-bezoar, and artificial cow-bezoar could be differentiated by the existence of hyodeoxycholic acid and the ratio of cholic acid to deoxycholic acid. This study provided bile acid profiles of bile-based Chinese medicines for the first time, which could be used for their quality control. (C) 2010 Elsevier B.V. All rights reserved.

So far, the components responsible for the neuroprotective effects of are unclear. Cholesterol, one of the major components in , is easily oxidized into oxysterols, which possess direct or indirect neuroprotective effects proved by our and others’ previous studies. Therefore, a liquid chromatography with mass spectrometry method coupled with ultrasonic extraction and solid‐phase extraction was developed for the determination of neuroprotective oxysterols in , human gallstones, and traditional Chinese medicine preparations. Chromatographic separation was achieved on a Ccolumn with isocratic elution at a flow rate of 1 mL/min. The established method showed good linearity (> 0.998), sensitivity with low limits of detection (0.06–0.39 μg/g), acceptable precisions (relative standard deviations ≤ 7.4%), stability (relative standard deviations ≤ 5.9%), and satisfactory accuracy (92.4–102.9%) for all analytes identified by different retention times, which could be applied for the determination of oxysterols. Five kinds of oxysterols proved to function as neuroprotectants were detected at different concentrations. Among them, 7β‐hydroxycholesterol and cholestane‐3β,5α,6β‐triol were rather abundant in the samples. It could be concluded that the potential neuroprotective components in may be these oxysterols.

Major bioactive components in various Calculus Bovis, including natural, artificial and in-vitro cultured Calculus Bovis, were comparatively studied. An approach of high-performance liquid chromatography coupled with ultraviolet and evaporative light scattering detections (HPLC/UV/ELSD) was established to simultaneously determinate six bioactive components thereof, including five bile acids (cholic acid, deoxycholic acid, ursodeoxycholic, chenodeoxycholic acid, hyodeoxycholic acid) and bilirubin. ELSD and UV detector were applied to detect bile acids and bilirubin respectively. The assay was performed on a C(18) column with water-acetonitrile gradient elution and the investigated constituents were authenticated by comparing retention times and mass spectra with those of reference compounds. The proposed method was applied to analyze twenty-one Calculus Bovis extraction samples, and produced data with acceptable linearity, precision, repeatability and accuracy. The result indicated the variations among Calculus Bovis samples under different developmental conditions. Artificial and in-vitro cultured Calculus Bovis, especially in-vitro cultured ones, which contain total bioactive constituents no less than natural products and have the best batch-to-batch uniformity, suffice to be used as substitutes of natural Calculus Bovis.

Artificial Calculus Bovis is a major substitute in clinical treatment for Niuhuang, a widely used, efficacious but rare traditional Chinese medicine. However, its chemical structures and the physicochemical properties of its components are complicated, which causes difficulty in establishing a set of effective and comprehensive methods for its identification and quality control. In this study, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry method was successfully developed and validated for the simultaneous determination of bilirubin, taurine and major bile acids (including six unconjugated bile acids, two glycine-conjugated bile acids and three taurine-conjugated bile acids) in artificial Calculus Bovis using a Zorbax SB-C18 column with a gradient elution of methanol and 10 mmol/L ammonium acetate in aqueous solution (adjusted to pH 3.0 with formic acid). The mass spectra were obtained in the negative ion mode using dehydrocholic acid as the internal standard. The content of each analyte in artificial Calculus Bovis was determined by monitoring specific ion pairs in the selected reaction monitoring mode. All analytes demonstrated perfect linearity (r(2) > 0.994) in a wide dynamic range, and 10 batches of samples from different sources were further analyzed. This study provided a comprehensive method for the quality control of artificial Calculus Bovis.

目的通过模拟人体胃肠消化液条件,比较不同溶出介质中动物结石药物牛黄及其代用品人工牛黄中胆汁酸类成分的溶出量差异,从体外溶出的角度探讨影响难溶中药疗效的可能因素。方法分别取同一批天然牛黄、人工牛黄,分别加入3种不同溶出介质(人工胃液、小肠液、大肠液),平行提取处理,以UPLC法测定胆汁酸类成分的溶出量,以甲醇中的溶出量为参比,计算各胆汁酸成分的相对溶出率。液相检测色谱柱为WatersAcquityCSH柱(50mm×2.1mm,1.7μm),流动相为乙腈(A)-0.2%甲酸-水(B),线性梯度洗脱:0～2分钟,10%A;2～3分钟,12%～25%A;3～3.01分钟,25%～35%A;3.01～10分钟,35%～37%A;10～17分钟,37%～43%A;17～17.01分钟,43%～48%A;17.01～20分钟,48%～52%A。检测波长254nm,流速0.4ml/min,柱温35℃。结果牛黄中胆汁酸类成分在人工大肠液(pH7.6)中溶出率高于人工胃液和小肠液;天然牛黄中,除去氧胆酸外,各胆汁酸成分的溶出率均高于人工牛黄,其中鹅去氧胆酸相差9.13倍;天然牛黄中甘氨胆酸、甘氨去氧胆酸和鹅去氧胆酸溶出率较高,而现行药典质量控制指标胆酸的溶出较差。结论以胆汁酸类成分来看,天然牛黄溶出能力高于人工牛黄,可能是人工牛黄临床疗效低于天然牛黄的原因之一。加强难溶性中药的溶出研究,对提高相关制剂的疗效、节约药材等具有重要意义。

胆红素是生化研究的重要试剂,也是制药工业的重要原料,它具有祛痰、镇静、拟菌、降压的作用,又有促进红细胞再生、拟制癌细胞的作用。文章主要对胆红素提取工艺及条件、工艺流程进行探讨,以提高胆红素产量。

作为久负盛名的中药急救药品,安宫牛黄丸协同其他疗法对脑炎,中风,脑出血、脑缺血性损伤等脑病及所导致 的高热昏迷有独特的疗效,现代药理实验表明安宫牛黄丸对大鼠急性期脑出血、脑缺血损伤有较好的保护作用,对闭合性脑损伤大鼠的脑水肿、脑缺血缺氧状态等有 一定的积极作用,另外安宫牛黄丸对脓毒症大鼠也有一定的干预作用.但由于安宫牛黄丸组方中含有雄黄(砷)和朱砂(汞),其安全服用尤为重要,本文从安宫牛 黄丸的现代药理作用、临床应用等方面阐述它的研究现状,旨在为合理应用安宫牛黄丸提供新的思路和参考.

正 安宫牛黄丸具有清热解毒、辟秽通窍、镇静安神的功效,用以治疗温邪内陷,高热烦躁,神昏谵语,抽搐惊厥,疗效显著。长期以来,它与局方至宝丹、紫雪丹并被誉为抢救温病重症的“三宝”,为我国医药界所熟知的著名中成药之一。但是,由于其所含的某些药物,来源

1) Sulfathiazole forms eutectic mixtures with urea, l-ascorbic acid, acetamide, nicotinic acid, nicotinamide, or succinimide. It was observed that a eutectic mixture of sulfathiazole and urea produces a microcrystalline suspension of sulfathiazole in water. 2) Sulfathiazole in a eutectic mixture with urea shows higher absorption and excretion after oral administration than ordinary sulfathiazole. 3) Since urea does not possess solubilizing action on sulfathiazole and also it does not enhance absorption of the drug physiologically, the accelerated absorption or excretion must be attributed to the physical state of sulfathiazole in its eutectic mixture with easily soluble compound, such as urea. 4) It is assumed that this new form of preparation will give a means of adjusting therapeutic effect of medical compounds.

目的:优选西黄滴丸的成型工艺.方法:以滴丸的溶散时限、外观质量及丸重差异为综合评价指标,在单因素试 验基础上,选取药物与基质的配比、滴制温度、冷却剂温度、滴距为考察因素,采用正交试验优选西黄滴丸的成型工艺.结果:最佳成型工艺条件为以 PEG8000-PEG10000(1∶1)为基质,药物-基质(1:1.5),冷却剂为二甲基硅油100,药液温度75℃,冷却剂温度采用梯度冷却方式 (上部温度30℃,下部温度0～5℃),滴速20 ～ 25滴/min,滴距4 cm.结论:优选的西黄滴丸成型工艺合理、稳定可行,为西黄滴丸的临床推广提供参考.

目的 研究西黄丸滴丸抗肿瘤作用及对免疫功能的影响.方法 将H22荷瘤小鼠模型分为模型组、西黄丸组、西黄丸滴丸不同剂量组,干预10 d后,测定各组小鼠的脾指数和胸腺指数,ELISA法测定小鼠血清中TNF-α、IL-1、IL-6、INF-γ含量.结果 西黄丸滴丸低、中、高剂量均对H22荷瘤小鼠具有明显的抑瘤作用,其抑瘤率分别为62.45％、70.61％、76.93％；各剂量西黄丸滴丸均能提高免 疫器官的质量及血清中TNF-α、IL-1、IL-6、INF-γ含量.结论 西黄丸滴丸具有明显的抑制肿瘤生长和增强机体免疫功能作用.

探讨近年来超微粉碎技术的研究进展。介绍超微粉碎技术对粉末性质、有效成分提取以及药动学方面的影响，并且对超微粉碎技术存在的弊端给出思考和建议。超微粉碎技术研磨出的粉体粒度小而均匀，能够增加药物有效成分的溶出度，促进药物在体内的吸收。超微粉碎技术提高了药物的生物利用度和药物的品质。

目的探索珍珠、牛黄普通粉和超细粉间理化特性的差异.方法通过粒径、分布宽度、松密度、休止角及比表面积 测定等方法对其普通粉和超细粉体进行表征.结果与普通粉相比,超细粉体颗粒大小均匀,平均粒径d90小于30 μm,较普通粉降低6.9～16.5倍;松密度下降;比表面积提高2.4～5.4倍.结论珍珠、牛黄经超细粉碎后,颗粒大小分布均匀,球性度及均质度明显 改善;粉体孔隙率增加,流动性增强,比表面积显著提高,从而使药物与机体亲和力变大,化学反应速率增加,药物的疗效大大提高.

目的:研究西黄软胶囊的抑瘤作 用,并探讨其抑瘤机制。方法:建立移植性S180肉瘤小鼠模型,观察西黄软胶囊对小鼠抑瘤率、脾指数、胸腺指数的影响,采用流式细胞仪检测西黄软胶囊对荷 瘤小鼠外周血T细胞亚群的影响。结果:西黄软胶囊各剂量组对S180肉瘤小鼠均有明显的抑瘤作用,增加荷瘤小鼠的脾指数、胸腺指数,显著性提高CD4+与 CD8+T细胞数目,升高CD4+/CD8+。结论:西黄软胶囊有明显的抗肿瘤作用,其机制可能是通过增强荷瘤小鼠的免疫功能来实现的。

粉末今的一个重要分支，其在药物制剂领域的应用优势突出，近年来受到药剂学研究者的广泛关注。分类综述目前应用于药物制剂的几种主要粉末包衣技术，包括属于物理化学法中的凝聚法、以及物理机械法中的喷雾干燥法、喷雾冷凝法、干法包衣技术和气流悬浮包衣技术，并探讨粉末包衣技术的主要功用，如用于制备缓控释制剂、药物粉末表面改性、改善口服制剂感官效果和提高药物及制剂稳定性等。

目的:为提高牛黄清感胶囊的稳定性,保证药品的质量.方法:采用正交设计法,以尤特奇EPO水分散体作为 包衣材料,对内容物中的中药浸膏粉进行粉末包衣工艺进行优选.结果:中药浸膏粉最佳包衣工艺条件:是采用底喷包衣,包衣进风温度35℃,喷气压力 0.1MPa,喷液速率4.Sg/min,包衣增重40％,重复包衣4次.结论:可有效提高产品质量.

脂质体作为一种新型的药物载体,具有靶向性,可提高药物的治疗指数和疗效,降低药物的毒性,缓释药物,保护被包封的药物等,采用脂质体作为药物载体是目前国际研究的热点.综合近年来脂质体技术在中药制剂及中药复方等方面的应用并对其进一步的发展做出展望.

文章从纳米技术出发，介绍了纳米技术的核心和本质，及其在制药工程中的应用背景；分析了药物制剂中的纳米粒类型，并分别详细阐述，最后讨论了纳米药物制剂比普通药物制剂具有的更多优良性状。

纳米技术在中药领域的应用与发展是中药走向国际化与现代化的有效途径.中药产生的药效并非仅仅取决于药物 的化学成分,还与药物的物理状态(如颗粒大小)有关,当药物处于纳米级时常会呈现新的药效,将纳米技术应用于中药中可拓宽中药的使用范围.介绍了纳米中药 的概念,对纳米中药的制备方法 、优势和发展方向等进行了综述,并分析了纳米中药发展中存在的问题,以及提出解决这些问题的设想,为纳米中药的发展提供新的思路.

Novel drug delivery systems have previously never been used in the formulation of any crude unfractionated traditional Chinese medicine. In the present study, a multi-unit drug delivery system (MUDDS) for a Chinese medicine Niuhuang Xingxiao Wan (NXW) was prepared using micro/nanotechnologies to enhance the bioavailability and efficacy. NXW was formulated into four units, that is, , and oil (FMO), , and . The four units were processed using the wet ball milling, high-pressure homogenization, liquid freezing-ultracentrifugation trituration, and dry grinding methods, respectively. After formulation, the four independent units prepared were encapsulated together to obtain the final NXW-MUDDS. Pharmacokinetic studies showed that the area under the plasma concentration-time curve (AUC), terminal half-life (T1/2), and time to reach the peak plasma concentration (Tmax) following administration of NXW-MUDDS were 5.21, 1.96, and 1.99 times higher, respectively, than that of NXW. The in vivo antitumor activity assay showed that the efficacy of NXW-MUDDS was significantly higher (P<0.05) than that of NXW. Collectively, these results reveal the feasibility of applying micro/nanotechnologies in formulating Chinese medicines.