化风丹的研究进展

化风丹是临床常用的中成药。本文对近年来化风丹在制剂工艺、质量控制、毒理作用、治疗作用、药物代谢动力学、药效物质基础及不良反应等方面的研究进展进行综述,为化风丹的深入研究提供参考。     

化风丹治疗脑卒中的疗效观察

目的研究化风丹治疗脑卒中的，临床疗效。方法选取2013年5月至2013年10月间入院诊治的脑卒中患者60例，随机分为实验组（30例）和对照组（30例），其中实验组应用化风丹治疗，对照组应用常规西药硫酸氯吡格雷治疗，观察两组疗效和不良反应。结果治疗前两组患者的FMA、ADL评分无差异。治疗后，实验组FMA评分为（63．1±4．3）分，对照组仅为（38．8±4．8）余实验组ADL评分为（78．5±5．5）分；对照组仅为（62．7±5．3）分；两组差异显著（P〈0．05）。实验组无不良反应；对照组1例出血，经对治疗后痊愈。结论应用化风丹治疗脑卒中疗效显著，不良反应少，可为临床治疗脑卒中提供一定的参考。     

小儿至宝丸中朱砂和雄黄的含量测定

摘 要 目的： 建立小儿至宝丸中朱砂和雄黄的含量测定方法。方法: 分别采用原子吸收分光光度法（AAS）和电感耦合等离子体发射光谱法（ICP-AES）测定小儿至宝丸朱砂中的汞和雄黄中的砷含量。结果: AAS法测定的汞的线性范围为5～100 μg·mL^-1（r=0.999 9）,砷的线性范围为2～50 μg·mL^-1（r=0.999 2）,汞的平均回收率为99.3%,RSD为3.0%（n=6）,砷的平均回收率为104.5%,RSD为2.1%（n=6）;ICP AES法测定的汞的线性范围为0.1～20.0 μg·mL^-1（r=0.999 97）,砷的线性范围为0.1～20.0 μg·mL^-1（r=0.999 99）,汞的平均回收率为96.6%,RSD为1.4%（n=6）,砷的平均回收率为104.1%,RSD为1.1%（n=6）。结论:本文建立的方法准确、专属性强,可用于控制小儿至宝丸中毒性成分的含量。     

规范朱砂、雄黄及相关成方制剂标准的思考

朱砂和雄黄在我国临床应用历史非常悠久,至今应用十分广泛,尤其是我国现行上市的中成药中,含有朱砂和雄黄的品种很多,如安宫牛黄丸、牛黄清心丸等等.而且,近年采雄黄在中医以毒攻毒理论指导下,还成功用于白血病的治疗.但是,随之临床应用的普反和推广,不良反应也日益增多,引起了国内外的广泛关注.如何安全、有效、合理的使用朱砂、雄黄以及舍有朱砂、雄黄的中成药,规范其八使用标准已是当前必须亟待解决的严重问题.本文分析朱砂、雄黄产生不良反应的原因,并指出需要时朱砂、雄黄在成药中药用价值进行再评定,且针对朱砂、雄黄存在的问题,提出了相应的对策.     

牛黄清心丸(局方)中朱砂和雄黄的含量测定

目的 建立牛黄清心丸(局方)中朱砂和雄黄的含量测定方法.方法 先对牛黄清心丸进行硝化处理,运用氧化还原滴定法分别以硫氰酸铵滴定液和碘滴定液对制剂中朱砂和雄黄的主要成分硫化汞和二硫化二砷进行定量分析.结果 硫化汞取样量在19.8～99 mg范围内与硫氰酸铵滴定液消耗体积呈良好的线性关系,回归方程为Y=85.5 X+0.046,r=0.999,平均加样回收率为101.07%,RSD为2.21%,硫化汞含量为57.75 mg/丸;二硫化二砷取样量在9.5～47.5 mg范围内与碘滴定液消耗体积呈良好的线性关系,回归方程为Y=171.83X-0.050 9,r=0.999,平均加样回收率为101.08%,RSD为1.10%,二硫化二砷含量为22.91 mg/丸.结论 所建立的方法可靠、准确性高、专属性强,可进一步控制该制剂的毒性成分含量.     

安宫牛黄丸及朱砂和雄黄对脂多糖诱导的神经损伤的作用(英文)

目的探讨朱砂和雄黄在安宫牛黄丸(AGNH)配方中对脂多糖(LPS)介导的神经损伤的保护作用及机制。方法制备大鼠中脑原代神经元-神经胶质细胞联合培养模型。实验分为正常对照组、LPS 10μg.L-1模型组、LPS +朱砂(4和40 mg.L-1)组、LPS +雄黄(4和40 mg.L-1)组和LPS +AGNH(40和400mg.L-1)组。药物与细胞作用30 min后加入LPS;7 d后进行实验指标检测。采用免疫组织化学染色法检测酪氨酸羟化酶阳性的细胞数量和形态学变化以及小神经胶质细胞的激活情况,实时RT-PCR检测细胞中肿瘤坏死因子α(TNF-α)mRNA和诱导型一氧化氮合酶(iNOS)mRNA表达水平,酶联免疫吸附试验(ELISA)与Griess试剂分别检测细胞培养上清液中TNF-α和一氧化氮(NO)的含量。结果与正常对照组比较,LPS10μg.L-1作用于细胞,多巴胺能神经元的数量明显下降了40%(P<0.05);LPS显著诱导小神经胶质细胞的激活,TNF-αmRNA和iNOS mRNA的表达分别增加了9倍和2倍(P<0.05),同时神经元-胶质细胞联合培养上清液中TNF-α和NO的含量分别增加了20倍和30倍(P<0.05)。与LPS模型组比较,AGNH400mg.L-1和雄黄40 mg.L-1能明显拮抗LPS对多巴胺能神经元的毒性作用,多巴胺神经元数量分别上升了40%和30%(P<0.05);AGNH400 mg.L-1和雄黄40 mg.L-1能抑制小神经胶质细胞的激活,小胶质神经细胞中TNF-αmRNA分别下降了61%和52%(P<0.05)和iNOS mRNA的表达分别降低了58%和51%(P<0.05),而且神经元-神经胶质细胞联合培养上清液中TNF-α的含量分别降低了55%和43%(P<0.05)以及NO的含量分别下降了53%和34%(P<0.05)。而朱砂对LPS的作用无影响。结论 AGNH能改善LPS介导的神经元损伤,雄黄是其抗炎作用的有效成分之一,朱砂未见明显的神经保护作用。     

应加强对朱砂、雄黄药用价值的再评价

<正>一、问题的提出朱砂含汞,雄黄含砷,都是国际社会严格限用于药品中的成分。成方制剂因含朱砂、雄黄被外国禁用,不仅严重影响出口创汇,也严重损坏中药的声誉。鉴于朱砂、雄黄是著名的传统药物,在历史上有过贡献,现在朱砂、雄黄依然列入国家药典,列入现行四大国家标准含朱砂、雄黄的成方制剂多达440种(含朱砂的247种,含雄黄的78     

对《中国药典》一部含朱砂、雄黄成方制剂有关问题的商榷

朱砂、雄黄均为有毒中药，其主要成分分别为硫化汞（HgS）和二硫化二砷（As2S2）。现代药理研究表明，汞和砷均为细胞原浆毒。汞、砷化合物与体内酶蛋白的巯基具有特异的亲和力，可使酶失去活性，影响细胞正常代谢，导致细胞死亡，因而引起神经系统及其他系统的功能与器质性病变。含朱砂、雄黄的中成药中均有可溶性汞和游离汞及三氧化三砷存在。     

一些用了几千年的中药不一定就安全——政协委员建议对朱砂、雄黄的药用价值和安全性进行再评价

中医药以矿物入药的历史悠久．重镇安神的朱砂、辟蛇蝎毒虫的雄黄就是其中的代表。现行四大国家标准中．含朱砂、雄黄的成方制剂多达440种，占所收载的全部成方制剂的6．34％，其中不乏安宫牛黄丸、牛黄解毒丸等经典名药。近年来，随着人们对药品不良反应的日益重视，中药朱砂、雄黄的不良反应问题逐渐浮出水面。全国政协委员、中国中医科学院首席研究员周超凡在递交政协会议的提案中指出，尽管朱砂、雄黄已经用了几千年，但由于历史条件的限制，临床对于朱砂、雄黄的药用价值和不良反应问题都不很清楚，目前亟待对其进行再评价。这不仅关系到朱砂、雄黄的药用前景，也关系到如何继承和发扬传统医药学这样一个大问题。[第一段]     

化风丹联合基础方案治疗中风有效性和安全性Meta分析

目的 评价化风丹联合基础方案(包括西医疗法、针刺等)治疗中风的有效性和安全性.方法 计算机检索中国期刊全文数据库、万方数据库、维普期刊全文数据库,以及PubMed,Web of Science,The Cochrane Library数据库,检索时限为各数据库自建库起至2021年8月23日.收集化风丹治疗中风的随机对照...     

雄黄及其复方的毒理学研究进展

中药雄黄主要成分为四硫化四砷。作为含砷矿物类中药,雄黄及其复方的毒性问题近年来倍受关注,其应用在国外也遭到了限制甚至禁止。因此,为全面正确认识雄黄及其复方的毒性,人们对其急性毒性、长期毒性、特殊毒性以及炮制、给药剂量和给药时间与毒性的关系等进行了大量的毒理学研究。此外,雄黄的毒代动力学、雄黄及其复方与化学形式的砷剂(如砷酸钠)的毒性比较等也得到了相关的毒理学研究。本文对雄黄及其复方的毒理学研究现状进行概述,对研究中存在的问题进行分析总结,并在此基础上提出了进一步研究的方向。     

朱砂及含朱砂制剂的肝肾毒性研究

目的 探讨朱砂、含朱砂制剂（柏子养心片）及甲基汞对大鼠的体内外毒性,为其临床安全用药提供科学依据。方法 ①对比甲基汞、朱砂及柏子养心片体外对人肝HL-7702细胞和人肾近曲小管上皮HK2细胞的毒性,计算半数抑制浓度（IC₅₀）。②SD大鼠随机分为对照组,朱砂组0.1 g/kg,柏子养心片0.2、0.4、0.8 g/kg组,甲基汞组0.001 g/kg,每天ig 1次,连续给药90 d后,取血及肝、肾组织;试剂盒法检测血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肌酐（CREA）、尿素氮（BUN）水平,测汞仪固体直接进样法检测肝、肾组织中汞蓄积量,并对大鼠肝脏和肾脏做组织病理学检查。结果 体外试验表明,朱砂、柏子养心片及甲基汞对HL-7702细胞的IC₅₀分别为7.852、6.035、0.009 5 g/L;对HK2细胞的IC₅₀分别为6.297、4.484、0.008 9 g/L。亚慢性毒性试验表明,甲基汞组大鼠肝、肾组织中汞蓄积量及血清中ALT、AST、CREA、BUN值均显著高于对照组,而朱砂及柏子养心片（高、中、低剂量）组与对照组比较均没有显著性差异;甲基汞组大鼠肝脏呈现肝细胞变性,肾脏可见明显肾小管损伤,而朱砂及柏子养心片（高、中、低剂量）组与对照比较没有明显差异。结论 朱砂及柏子养心片的体内外毒性均显著低于甲基汞,在目前药典规定的临床用量下使用安全性较好。     

Neurotoxic mechanism of cinnabar and mercuric sulfide on the vestibulo-ocular reflex system of guinea pigs.

Cinnabar, a naturally occurring mercuric sulfide (HgS), has been combined with Chinese herbal medicine as a sedative for more than 2000 years. To date, its neurotoxic effect on the vestibulo-ocular reflex (VOR) system has not been reported. By means of a caloric test coupled with electronystagmographic recordings, the effect of commercial HgS and cinnabar on the VOR system of guinea pigs was studied. HgS or cinnabar was administered orally (1.0 g/kg) to Hartley-strain guinea pigs once daily for 7 consecutive days. A battery of electrophysiological, biochemical, and histopathological examinations were performed. The results showed that HgS induced a 60% caloric response abnormality (40% caloric hyperfunction and 20% hypofunction), whereas the abnormal responses appeared to be more severe (six out of six) in the cinnabar group. The Hg contents of whole blood and cerebellum were increased and correlated to their neurotoxic effects on the VOR system, indicating that both insoluble HgS and cinnabar could be absorbed from the gastrointestinal tract and distributed to the cerebellum. Although the vestibular labyrinth revealed no remarkable change under light microscopy, loss of Purkinje cells in the cerebellum was detected, and the enzymatic Na(+)/K(+)-ATPase activity of cerebellum (a higher inhibitory center of the VOR system) was significantly inhibited by HgS and cinnabar. Moreover, cerebellar nitric oxide (NO) production was increased significantly. Hence, we tentatively conclude that the increased Hg contents in the cerebellum following oral administration of HgS and cinnabar were responsible, at least in part, for the detrimental neurotoxic effect on the VOR system. Potentially, decreasing Na(+)/K(+)-ATPase activity and increasing NO production within the cerebellar regulatory center are postulated to mediate this VOR dysfunction caused by the mercurial compounds and cinnabar.     

Chronic toxicity and bioaccumulation of mercuric chloride in the fathead minnow (Pimephales promelas)

Fathead minnows (Pimephales promelas) were exposed to various concentrations of mercuric chloride in water to determine its acute and chronic (including reproduction) toxicity and to measure bioaccimulalion. Mean LC₅₀ values of HgCl₂ for juvenile fatheads were 168, 112, 84, and 74 μg Hg/l at 4, 5, 6, and 7 days, respectively. Following 41 wk of exposure to 0.26 to 3.69 μg/l, females were significantly smaller than controls at all concentrations except 0.50 μg/l and males showed reduced growth at 3.69 μg/l. Over half of the fish at 2.01 and 3.69 μg/l were severely stunted and scoliosis was prevalent among these stunted fish. No spawning occurred at and above 1.02 μg/l and the number of spawning pairs was reduced at 0.26 and 0.50 μg/l resulting in total egg production of 46 and 54%, respectively, of control. Thirty-day growth of second-generation larvae (from transferred control embryos at and above 1.02 μg/l) was significantly reduced at all mercury concentrations tested. No effects on hatchability or larval survival were detected. Chronically-exposed fish accumulated mean whole body total mercury residues of 1.36 to 18,80 μg/g of tissue (wet weight) from 0.26 to 3.69 μg/l, respectively. Uptake appeared proportional to water concentration; bioconcentration factors varied between 4380 and 5680.The influence of diet on mercury toxicity and bioaccumulation was studied during two 60-day larval fathead exposures. Overall recuccd growth and possibly enhanced toxic effects occurred in larvae on the dry trout starter diet compared to larvae fed on Artemia. Mercury uptake appeared influenced by the severity of toxic effects.     

两种急性肾衰家兔模型的酚红药动学比较

目的比较甘油和氯化汞所诱发的急性肾衰模型对家兔酚红药动学的影响,为选择较佳的肾小管衰竭模型提供依据。方法家兔随意分成正常组,以及甘油和氯化汞诱发的两个急性肾衰模型组。静脉注射1.2 mg.kg-1酚红后,测定血药浓度,计算酚红药动学参数。结果与正常组比较,甘油和氯化汞诱发的肾衰模型组的血清尿素氮(blood urea nitrogen,BUN)和肌酐(creatinine,Cr)显著性增高(P<0.01),氯化汞组的BUN和Cr较甘油组增高约3.8倍(P<0.01),各组之间的c(BUN):c(Cr)无显著性差异。与正常组比较,2个模型组的消除速率常数(kel)显著性下降(P<0.01),消除半衰期(t1/2)显著性延长(P<0.01),以氯化汞组的变化更显著。模型组的酚红总清除率(CLt)较正常组显著性减少(P<0.01)。氯化汞组的表观分布容积(Vd)较甘油组和正常组显著性增大(P<0.01)。结论 2种模型组均可导致肾小管排泌功能下降,氯化汞所致的急性肾衰更显著。     

原子吸收分光光度法测定桃花散中朱砂与石膏的含量

目的：建立测定桃花散中朱砂、石膏的含量测定方法。方法：湿法消解样品,采用原子吸收分光光度法测定汞和钙含量后换算。结果：加样回收率为（９９８±２０）％和（９９６±２２）％。结论：本法操作简便,结果准确精密。可用于桃花散的定量标准。     

Acute toxicity of monochlorophenols, dichlorophenols and pentachlorophenol in the mouse

Acute oral LD50 values were determined for 2-, 3-, and 4-chlorophenol, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5 dichlorophenol and pentachlorophenol in male and female mice. LD50 values (mg/kg) ranged from 117 (females) and 177 (males) for pentachlorophenol to 2389 (females) and 2643 (males) for 3,5-dichlorophenol. It was found that 2-chlorophenol and 3-chlorophenol were considerably more toxic than the dichlorophenol series. Values for males and females were generally similar, the major differences being with pentachlorophenol and 2,5-dichlorophenol, where in both cases the female LD50 was lower.     

Acute and subacute (28-Day) toxicity studies of ionic liquid,didecyldimethyl ammonium acesulfamate,in rats

The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD₅₀ cut-off value of 500?mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100?mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10?mg/kg/day.