弱碱性蒽贝素氨水溶液小鼠尾静脉注射急性毒性实验研究

目的研究小鼠尾静脉注射弱碱性蒽贝素氨水溶液的急性毒性反应,测定经该途径给药后,小鼠半数致死剂量及其99%平均可信限。方法小鼠尾静脉注射弱碱性蒽贝素氨水溶液,预试出最大0%和最小100%致死剂量。再分别给12组小鼠尾静脉注射按1:0.8等比稀释的系列浓度溶液0.01 m L·g-1,剂量在最大0%致死剂量和最小100%致死剂量之间,观察给药后7日内各组小鼠中毒死亡情况。解剖检查死亡小鼠主要器官。计算半数致死剂量及其99%平均可信限。结果给药剂量在60~448 mg·kg-1间时,最低、最高剂量组小鼠死亡率介于30%和70%之间,剂量对数与死亡机率单位之间呈近似线性关系,可以用综合法计算半数致死剂量及其99%平均可信限。结论以蒽贝素量计,尾静脉注射弱碱性蒽贝素氨水溶液小鼠半数致死剂量为153.525 mg·kg-1,其99%平均可信限为153.525±40.815 mg·kg-1。     

玉叶清火胶囊中玉叶金花鉴别方法的研究

目的:考查玉叶清火胶囊中玉叶金花的鉴别方法。方法:通过改变提取方法、洗脱剂、展开剂选择薄层色谱法(TLC)中的最佳实验条件。结果:经大孔树脂处理,20%～30%之间的乙醇洗脱,以三氯甲烷-甲醇-水(13:6:2)10℃以下放置分层的下层溶液为展开剂得到的薄层色谱图中,玉叶金花与对照药材色谱在相应的位置上,显相同颜色的斑点,且斑点清晰,分离效果好,阴性对照无干扰。结论:实验证明此方法简便、快捷,能准确鉴别出玉叶清火胶囊中的玉叶金花。     

广西“玉叶金花属”植物八种玉叶金花的生药学研究

目的:对广西"玉叶金花属"植物八种玉叶金花进行生药学研究.方法:采用性状、显微鉴定及薄层鉴别的方法.结果:八种玉叶金花在性状上存在一定差异,但在显微特征及薄层色谱上无明显差异.结论:从性状、显微及薄层鉴别3个角度看,八种玉叶金花均可作为玉叶金花提供药用.     

茶酚硒混合物的小鼠急性毒性试验

目的:观察茶多酚(TP)与亚硒酸钠(sodium selenite)混合物一次给予小鼠的急性毒性反应和死亡情况.方法:一次灌胃(ig)给药,观察14d.结果:测得TP单用一次ig的LD50为2914.45mg/kg;亚硒酸钠单用一次ig的LD50为33.54mg/kg;当TP与亚硒酸钠按7997.3mg∶2.7mg比例做成混合物,测得混合物单次ig的LD50为2510.29mg/kg,其中亚硒酸钠的含量为0.85mg/kg.结论:茶酚硒混合物单次ig的LD50为2510.29mg/kg.     

茶酚硒混合物的小鼠急性毒性试验

目的:观察茶多酚(TP)与亚硒酸钠(sodium selenite)混合物一次给予小鼠的急性毒性反应和死亡情况.方法:一次灌胃(ig)给药,观察14d.结果:测得TP单用一次ig的LD50为2914.45mg/kg;亚硒酸钠单用一次ig的LD50为33.54mg/kg;当TP与亚硒酸钠按7997.3mg∶2.7mg比例做成混合物,测得混合物单次ig的LD50为2510.29mg/kg,其中亚硒酸钠的含量为0.85mg/kg.结论:茶酚硒混合物单次ig的LD50为2510.29mg/kg.     

基于均匀设计法的钩吻配伍玉叶金花的毒性作用规律研究

目的 探讨钩吻配伍玉叶金花后的毒性变化规律。方法 采用U₇^*(7⁴)均匀设计表,按2因素7水平设计配比实验,以小鼠死亡率为考察指标进行急性毒性评价,并考察钩吻配伍前后的LD₅₀。结果 均匀设计得到的多元函数模型具有显著性统计学意义(P<0.05),针对函数模型求偏导得最佳配比0.54∶14.23(钩吻∶玉叶金花),三维曲面分析的低毒性的剂量配比范围(钩吻∶玉叶金花= 1∶22~36);钩吻LD50为0.32 g·kg^-1,而配伍后LD50为0.68 g·kg^-1,毒性大幅降低。结论 钩吻配伍玉叶金花后毒性降低,可为临床合理用药提供参考依据。     

斑马鱼胚胎急性毒性和小鼠急性经口毒性测试方法的相关性研究

传统的毒理学安全性评价方法主要采用大鼠、小鼠和兔子等作为受试实验动物来进行体内实验,获取相关毒理学毒性数据.然而,啮齿类动物毒性检测的周期长、花费高,且随着动物实验3R原则的推广,逐渐限制了现代生物医药和食品行业中大规模使用动物试验来进行毒理学安全性评价.     

大孔树脂纯化玉叶金花中三萜皂苷mussaendoside G的工艺研究

目的优选大孔树脂分离纯化玉叶金花中三萜皂苷mussaendoside G的工艺条件。方法通过静态与动态的吸附-解析2种方法比较5种不同类型大孔树脂对玉叶金花三萜皂苷的吸附性能,采用HPLC方法测定,以mussaendoside G的含量为评价指标,进行工艺筛选。结果 01G3型大孔树脂为最优;最佳工艺为上样浓度为1 g(生药材)·m L-1,上样量为1.5 m L·g-1(树脂重);1 m L·min-1流速,依次采用9 BV水、6 BV 20%乙醇、13 BV 60%乙醇和6 BV 95%乙醇洗脱;经优选工艺验证玉叶金花中三萜皂苷mussaendoside G平均得率达到92.21%。结论 01G3型大孔树脂能够较好地纯化富集玉叶金花中三萜皂苷mussaendoside G。     

百草枯对小鼠的急性毒性试验

目的 观察百草枯(Paraquat,PQ)对小鼠的急性毒性,计算其半数致死量(LD50).方法 给小鼠灌服不同浓度的PQ溶液,通过观察小鼠的活动和毒性反应,记录小鼠的死亡数,用概率单位法计算LD50.结果 给药后不同时间内,小鼠出现自由活动减少,濒死时呼吸频率加快、张口呼吸、鼻翼扇动等中毒症状,死亡高峰在2 h内,死亡原因为多脏器损伤.♂小鼠LD50=106.99 mg·kg-1,95%可信限范围为97.01～118.03 mg·kg-1;♀小鼠LD50=86.40 mg·kg-1,95%可信限范围74.54～100.14 mg·kg-1.结论 PQ属于中等毒农药,♀小鼠更敏感.     

玉叶金花总皂苷指纹图谱及其肝保护作用的谱效关系研究

目的 建立玉叶金花总皂苷指纹图谱,并进行其肝保护作用的谱效关系研究。方法 取不同产地的玉叶金花药材,以75%乙醇为溶剂,制备10批玉叶金花总皂苷。采用高效液相色谱法测定,利用《中药色谱指纹图谱相似度评价系统（2012版）》绘制10批玉叶金花总皂苷的指纹图谱,并进行相似度评价、共有峰指认。采用同一高效液相色谱法,测定其中5种三萜皂苷类成分（mussaendoside H、mussaendoside U、mussaglaoside C、mussaendoside G、mussaendoside O）的含量。以四氯化碳致急性肝损伤小鼠模型考察玉叶金花总皂苷的肝保护作用,并通过灰色关联度分析法进行谱效关系研究。结果 10批玉叶金花总皂苷共有11个共有峰,指认了其中5个,分别为mussaendoside H(3号峰)、mussaendoside U(7号峰)、mussaglaoside C(8号峰)、mussaendoside G(9号峰)、mussaendoside O(11号峰);10批样品的相似度为0.940～0.991。mussaendoside H、mussaendoside U、mu...     

小鼠静脉注射邻苯二甲酸丁基苄酯的毒物动力学

目的　研究氚标记的环境激素邻苯二甲酸丁基苄酯 (BBP)单次静脉注射后在其雄、雌小鼠体内的动力学过程的差异。方法　雄、雌小鼠各 3 0只 ,每组性别小鼠分 3组 ,每组 10只。静脉注射 10和 10 0mg kg3H -BBP后 ,用液闪仪检测给予一定时间后 ,检测在血清及各脏器中的放射性浓度 ,用NDST2 1药代动力学处理软件判断房室模型 ,计算各种参数。结果　3H- BBP单次静脉注射后在小鼠体内呈一级动力学线性过程 ,符合二室开放模型 ,3H- BBP在雄性小鼠的组织脏器内被大量摄取 ,以肝脏及性腺居高 ,蓄积性明显高于雌性。3H- BBP主要经尿排泄 ,并集中在 8h之内排泄 ,4d之内排泄量占注入量的 80 %左右。结论　静脉注射3H -BBP在雌、雄小鼠体内的动力学过程有明显的差异。     

Acute intravenous injection toxicity of BMEDA in mice

(188)Re/(186)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine-labeled pegylated liposome ((188)Re-BMEDA-liposome) has been proven as a promising candidate for cancer therapy in tumor-rodent models. (188)Re-BMEDA complexes should be prepared for the radiolabeling of liposomes. This article describes the acute toxicity of BMEDA in Imprinting Control Region (ICR) mice. Treated mice were administered with BMEDA at dose levels of 3, 6, 9, and 12?mg/kg, with a dose volume of 10?mL/kg. The control mice were administered 10?mL/kg of vehicle control. The mice were observed for 14 days. Observations included mortality, clinical signs, total body-weight gains, food consumption, and gross necropsy findings. BMEDA exerted no adverse toxic effects in ICR mice at dose levels 3?mg/kg, which are up to 360,000 times higher than the intended human dose. The lethal-dose (LD(50)) value of BMEDA was 8.13 and 8.68?mg/kg in male and female mice, respectively.     

Retinal toxicity of chloroquine hydrochloride administered by intraperitoneal injection

Chloroquine is quinolone derivative known to exert dose-related retinal toxicity, albeit in a variable manner. It is thought that variability in the presentation of chloroquine retinopathy may be the result of perturbations in drug bioavailability subsequent to oral ingestion. In order to better understand the ramifications of bioavailability on the development of retinal injury subsequent to chloroquine use, this study investigated the relationship between retinal injury and chloroquine administration via intraperitoneal rather than oral administration. Four-week-old C57/6J mice underwent daily intraperitoneal injection of 10 mg kg(-1) chloroquine hydrochloride for a total of 62 days. Following treatment, tissue was fixed in preparation for analysis by light and transmission electron microscopy. Treated animals demonstrated marked abnormality of the outer retinal layers described as complete loss of the outer plexiform layer as well as photoreceptors and photoreceptor nuclei. The retinal pigmented epithelium demonstrated focal atrophy, loss of nuclei and pigment irregularity. Findings in the inner retina were notable for the loss of Müller cells and the presence of membranous cytoplasmic bodies. Retinae of control animals were entirely normal. In contrast to previous studies in the murine model examining chloroquine retinopathy subsequent to oral administration, this study suggests that intraperitoneal chloroquine administration facilitates retinal toxicity, presumably due to heightened drug absorption and bioavailability. It is posited that an increased rate of drug accumulation within the retina leads to an enhanced lysosomotrophic drug effect due to inability of the lysosome to compensate for chloroquine-induced elevation in pH through re-acidification of the intra-lysosomal content.     

Lipophilicity affects the pharmacokinetics and toxicity of local anaesthetic agents administered by caudal block

1. Drugs administered into the epidural space by caudal block are cleared by means of a process potentially affected by the lipophilic character of the compounds. 2. In the present study, we examined the relationship between the octanol-water partition coefficient (log Poct) and the time to reach the maximum plasma drug concentration (tmax) of lignocaine, bupivacaine and ropivacaine administered by caudal block in paediatric patients. We also examined the relationship between log Poct and the toxicity of these local anaesthetic agents in experimental models. The tmax and toxicity data were obtained from the literature. 3. Ropivacaine, with a log Poct of 2.9, exhibited a tmax of 61.6 min. The tmax of lignocaine, with a log Poct of 2.4, and bupivacaine, with a log Poct of with 3.4, were approximately 50% shorter than ropivacaine. At log Poct of approximately 3.0, the toxicity of these local anaesthetic agents was substantially increased. The relationship between log Poct and the convulsive effect in dogs was similar to the relationship between log Poct and the lethal dose in sheep. 4. With local anaesthetic agents, it appears that the relationship between log Poct and drug transfer from the epidural space to the blood stream is parabolic, being the slowest rate of transference at log Poct 3.0. Toxicity, due to plasma availability of these local anaesthetic agents, seems to be increased at log Poct equal or higher than 3.0 secondary to the highest transfer from plasma into the central nervous system.     

喜炎平注射液在Beagle犬的急性毒性和长期毒性研究

目的对喜炎平注射液进行上市后的安全性再评价。方法给Beagle犬静脉输注喜炎平注射液,急性毒性:分为阴性对照组(n=2)及4个剂量(10,30,100,300 mg.kg-1)给药组(n=4);长期毒性:分为阴性对照组(n=6)及3个剂量(15,75,300 mg.kg-1)给药组(n=6)。结果急性毒性研究中各剂量组动物未见死亡。长期毒性研究中,Beagle犬出现了一过性呕吐、腹泻和注射部位的轻微病变。结论 Beagle犬对喜炎平注射液的最大耐受量为300 mg.kg-1。喜炎平注射液对Beagle犬的主要不良反应为胃肠道反应和注射部位反应。     

Acute intravenous injection toxicity study of IBZM and BZM in rats

S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (IBZM) is one of the several benzamide derivatives showing a high affinity for the central nervous system (CNS) D2 dopamine receptor. Carrier-free [123I]IBZM is potentially useful as a nuclear medicine imaging agent for investigating the CNS D2 dopamine receptor in humans. This study describes the acute toxicity of IBZM and S-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (BZM) in the rats. Treated rats were administered with IBZM at dose levels of 1 and 5 microg/kg and BZM at dose levels of 250 and 1250 microg/kg with dose volumes of 1 and 5 mL/kg. The control rats were administered 5 mL/kg of vehicle control. The rats were observed for 14 days. Observations included general demeanor, clinical signs, mortality, body weights/total body weight gains, and gross necropsy findings. None of the animals died during the 14-day study period. In female rats, the body weight gained at the first week of BZM treatment at a dose level of 1250 microg/kg and the total body weight gains of both IBZM treated groups were significantly higher than the control group (p < 0.05).     

Acute oral toxicity study of Asiasari radix extract in mice

Acute oral toxicity of methanol extract of Asiasari radix was evaluated in ICR mice of both sexes. In this study, mice were administrated orally with dosages of 1000, 3000, and 5000 mg/kg body weight of Asiasari radix extract. Mortality, signs of toxicity, body weight, food consumption, and gross findings were observed for 14 days post treatment of Asiasari radix extract. No mortality, signs of toxicity, and abnormalities in gross findings were observed. In addition, no significant differences were noticed in the body and organ weights between the control and treated groups of both sexes. These results show that the methanol extract of Asiasari radix is toxicologically safe by oral administration.     

替莫唑胺的小鼠急性毒性试验

目的观察替莫唑胺对小鼠的急性毒性。方法采用灌胃给药和腹腔注射给药两种途径进行试验,采用Bliss法计算半数致死量(LD50)。结果一次给药替莫唑胺可以对小鼠产生急性毒性,使小鼠陆续死亡,观察至给药后14d及以上仍有动物死亡。结论本品小鼠灌胃给药LD50为173.90mg/kg(95%的可信限为154.49～199.75mg/kg),腹腔注射给药LD50为164.53mg/kg(95%的可信限为144.36～187.49mg/kg)。     

Acute toxicity of intravenously administered microfabricated silicon dioxide drug delivery particles in mice: preliminary findings

BACKGROUND AND OBJECTIVE: Microfabricated particles with nanosized features may serve an important role in the next generation of drug delivery vehicles. Microfabrication (micro-electromechanical systems) technologies offer the promise of both structural elements (e.g., pores, reservoirs) and electromechanical features (e.g., timers, valves, actuators) built into a single particle. In order to serve as carriers to deliver drugs to systemic sites of action, such as tumors, the particles must be safe to administer intravenously. An acute safety study was performed in a mouse model, using intravenous injection of solid silicon dioxide particles created to simulate the size and shape of potential targeted drug delivery vehicles. DESIGN: Two-micron thick, square and circular, parallelepiped-shaped particles were produced with varying sizes of 2 microm, 5 microm and 10 microm using microfabrication techniques and injected into groups of mice (six mice per group) over a range of doses. End-points included acute lethality, clinical signs of toxicity and weight loss. Sections of major organs were sampled for histological examination. RESULTS: At dose levels of 1 x 10(8) particles per mouse, circular particles of 2 microm and 5 microm showed no signs of acute toxicity. Similar results were obtained with the 2 microm and 5 microm square silicon dioxide particles; however, 14-day necropsy indicates fewer 5 microm circular particles in the lung than 5 microm square particles, indicating that the shape of the particles may impact on safety. Acute lethality was observed for 10 microm particles; none of the mice injected with the 10 microm particles survived except at very low dose levels of 6 x 10(5) particles per mouse. CONCLUSIONS: Solid silicon particles greater than 5 microm in their largest dimension are cleared in the lungs and are not safe for intravenous delivery. Particles of 2-5 microm in size do not lodge predominantly in the lung and do not cause acute toxicity, but accumulate in organs such as the liver and spleen. Possible chronic toxicities associated with organ uptake of such non-biodegradable particles have yet to be addressed.