晕痛舒胶囊中川芎的鉴别研究

目的：建立晕痛舒胶囊质量标准中川芎的鉴别方法。方法：采用显微鉴别、薄层色谱鉴别及理化鉴别对方中川芎进行定性鉴别。结果：用薄层色谱鉴别,供试品色谱中,在与对照药材色谱相应的位置上显相同颜色的荧光斑点。色谱清晰,附近无杂质斑点干扰,显微鉴别特征虽明显,但是阴性样品有影响,理化鉴别显紫红色,阴性样品也出现相同现象。结论：采用薄层色谱法鉴别晕痛舒胶囊中的川芎,操作简便,专属性强,可更好地控制晕痛舒胶囊的质量。     

腰痛宁胶囊对小鼠的急性毒性试验研究

目的:观察小鼠口服腰痛宁胶囊的急性毒性作用。方法:采用Bliss法测定口服腰痛宁胶囊的LD50。结果:小鼠口服腰痛宁胶囊的胶囊LD50为622.6mg/kg,95%平均可信限为502.7～771.1mg/kg。结论:临床用药时应严格按照医嘱和药品说明书服用腰痛宁胶囊,以保证临床应用的安全。     

复方川芎胶囊活血作用研究

目的观察复方川芎胶囊改善微循环与血液流变学作用。方法①取SD大鼠60只,随机分为空白组,模型组,复方川芎胶囊低、中、高剂量组和复方丹参滴丸组各10只,各给药组分别灌胃给予复方丹参滴丸和低、中、高剂量复方川芎胶囊,qd,连续7 d,空白对照组给予等体积纯化水。于第7天皮下注射1 mg•mL 1盐酸肾上腺素（Adr）注射液,0.08 mL•（100 g） 1,共2次,两次间隔4 h。在两次注射Adr之间（前后各间隔2 h）将大鼠浸入冰水内5 min,制作血瘀模型,第7天处置后停食。各组大鼠均在第8天早晨用10%水醛0.3 mL•（100 g） 1腹腔麻醉,激光多普勒血流监测仪测定耳廓、大脑顶部及肠系膜血流灌注量。②取SD大鼠60只,同上述方法分组、造模后禁食,于次日清晨腹腔取血3 mL,迅速注入含肝素的抗凝管内,摇匀静置,检测血液流变学指标。结果复方川芎胶囊能改善血瘀模型大鼠耳廓、脑部、肠系膜微循环,显著降低血瘀模型大鼠全血黏度、红细胞聚集指数及变形指数,缩短红细胞电泳时间。结论复方川芎胶囊具有改善微循环和血液流变学的作用。     

参芎化瘀胶囊镇痛和镇静作用及急性毒性试验

目的:观察参芎化瘀胶囊(SXHYC)的镇静催眠和镇痛作用及急性毒性。方法:通过小鼠扭体法和小鼠热板法观察镇痛作用;并采用戊巴比妥钠阈下剂量致小鼠睡眠法,观察药物的镇静催眠作用;通过检测小鼠的最大耐受剂量,考察SXHYC的急性毒性。结果:SXHYC能抑制醋酸致小鼠扭体反应,提高小鼠热板法痛阈值。另外,SXHYC能提高戊巴比妥钠阈下剂量小鼠睡眠率。小鼠对SXHYC一日最大耐受剂量相当于成人临床用量的384倍。结论:SXHYC具有明显的镇痛和镇静作用,且急性用药安全。     

正交试验优选颅痛消胶囊制备工艺

目的:优选颅痛消胶囊的制备工艺。方法:以加水量、煎煮时间和煎煮次数为考察因素,以出膏率和川芎嗪含量为指标,采用正交试验优选提取工艺;测定休止角和临界相对湿度以控制生产条件。结果:优选的工艺为用15倍量的水煎煮3次,每次1.5h;可不加助流剂,环境相对湿度须<60%。结论:该工艺合理、可行,可为颅痛消胶囊的工业化生产提供理论依据。     

养血生发胶囊对小鼠急性毒性实验研究

目的 探讨养血生发胶囊对小鼠急性毒性的影响.方法 采用经典的急性毒性试验方法,进行养血生发胶囊对小鼠的急性毒性研究.结果 按生药量计算养血生发胶囊对小鼠的最大给药量(MLD)为24.0g·kg-1·d-1.相当于人日用剂量的420.0倍;给药后各小鼠急毒主要表现为安静、怠动,腹泻、毛色不华等毒性症状,给药后1天小鼠体重增长缓慢,与空白对照组有明显差异,给药后5天逐渐恢复,余未见明显异常,末次给药后2h血丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平明显增高,肝体比值增加.结论 养血生发胶囊小鼠急性毒性实验虽未做出LD50和MTD,小鼠也无一死亡,但给药后小鼠有肝功能损伤、肝体比值增加,提示在超大剂量灌胃后具有一定的肝毒性,与临床报道相一致.     

高效液相色谱法测定川芎胶囊中葛根素的含量

川芎胶囊为非标准自制制剂,由川芎及葛根两味中药组成,具有活血行气、祛风止痛、解肌生津等作用.对颈椎病、颈肌综合征、筋脉拘挛、高血压颈项强痛等有较好疗效.方中川芎性味辛温,有活血行气、祛风止痛之功效,对风寒湿痹及肢体关节疼痛有较好的疗效,为君药,其主要成分为阿魏酸[1],笔者曾对阿魏酸的含量进行测定,未得到理想分析方法,故不列入正文;葛根性味甘辛、平,具有解肌退热、生津、透疹、升阳止泻之功效,用于治疗颈背强痛及高血压颈项强痛,为臣药,其主要成分为葛根素[1],本文采用高效液相色谱法(HPLC)[2]测定葛根素的含量,目的是控制制剂质量,保证临床用药的有效性.     

祛风胶囊中白芍、川芎的薄层色谱鉴别

目的制定祛风胶囊的质量标准。方法采用薄层色谱法鉴别白芍、川芎。结果薄层色谱斑点清晰,重现性好,阴性对照无干扰。结论方法简便,准确,可供本品质量控制。     

高效液相色谱法测定川芎胶囊中葛根素的含量

川芎胶囊为非标准自制制剂,由川芎及葛根两味中药组成,具有活血行气、祛风止痛、解肌生津等作用.对颈椎病、颈肌综合征、筋脉拘挛、高血压颈项强痛等有较好疗效.方中川芎性味辛温,有活血行气、祛风止痛之功效,对风寒湿痹及肢体关节疼痛有较好的疗效,为君药,其主要成分为阿魏酸[1],笔者曾对阿魏酸的含量进行测定,未得到理想分析方法,故不列入正文;葛根性味甘辛、平,具有解肌退热、生津、透疹、升阳止泻之功效,用于治疗颈背强痛及高血压颈项强痛,为臣药,其主要成分为葛根素[1],本文采用高效液相色谱法(HPLC)[2]测定葛根素的含量,目的是控制制剂质量,保证临床用药的有效性.     

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.     

二巯丁二酸对小鼠的急性毒性作用

目的探讨二巯丁二酸（DMSA）对小鼠的急性毒性作用。方法20只昆明小鼠，雌雄各半，体质量（21．2±2．3）g，适应性喂养3d，按体质量随机分为对照组和实验组，给药前禁食12h，实验组每只小鼠于24h内分4次经口给予DMSA160mg，对照组给予等体积的去离子水，观察1周，然后摘除眼球取血，置于肝素化试管，5000r／min，离心5min，取血浆；处死小鼠，取其脑、心脏、肝脏和肾脏，0．9％氯化钠溶液清洗。测定抗氧化酶系统、过氧化产物、血尿素氮、血肌酐及氨基转移酶水平。结果（1）试验观察期内小鼠出现消化道症状，进食减少，体质量降低，腹腔轻度积水，此外未见其他明显中毒症状；（2）脑组织、肝脏和肾脏超氧化物歧化酶（SOD）活性降低，但差异无统计学意义（P〉0．05），谷胱甘肽过氧化物酶（GSH—PX）活性明显降低（P〈0．01），肝脏丙二醛（MDA）显著性升高（P〈0．01）；（3）血尿素氮和肌酐水平显著性升高（P〈0．001）；血氨基转移酶升高（P〈0．001），而肝肾氨基转移酶无显著性变化。结论二巯丁二酸抑制机体抗氧化系统，对肝脏和肾脏具有毒性作用。     

黑素再生颗粒的急性毒性实验研究

目的测定黑素再生颗粒对小鼠的急性毒性反应,为临床安全用药提供依据。方法实验组以黑素再生颗粒混悬液按0.3 mL.(10 g)-1体重24 h灌胃给药3次,对照组给予同体积的生活饮用水。观察并记录小鼠在给药后的行为活动、饮食、大便等情况及急性毒性反应和死亡数,连续观察7 d。结果小鼠在给药后观察期间状态良好,未出现明显毒性反应及死亡等情况。结论实验表明黑素再生颗粒毒性极低,临床使用安全性好。     

复方龙脷胶囊急性毒性实验研究

目的：观察复方龙脷胶囊的急性毒性反应,为临床安全用药提供实验依据.方法：采用小鼠灌胃给药测定复方龙脷胶囊的半数致死量（LD50）和最大给药量,观察其急性毒性作用.结果：LD50未测出,小鼠最大给药量为164.76g· kg-1 ·d-1,相当于成人临床日剂量的1 176.86倍,小鼠无死亡,未见异常急性毒性反应.结论：复方龙脷胶囊经小鼠灌胃给药无明显急性毒性反应.     

复方川芎胶囊联合阿罗洛尔治疗心绞痛的临床研究

目的 探讨复方川芎胶囊联合盐酸阿罗洛尔片治疗心绞痛的临床疗效.方法 选择2020年6月—2021年6月在濮阳市油田总医院治疗的118例心绞痛患者,根据用药的差别分为对照组和治疗组,每组各59例.对照组口服盐酸阿罗洛尔片,10 mg/次,1次/d;治疗组在对照组基础上口服复方川芎胶囊,4粒/次,3次/d.两组均经8周治疗...     

基因重组Kringle 5蛋白急性经口毒性试验研究

目的检测基因重组Kringle 5蛋白的急性经口毒性,为其临床应用提供医学毒理学依据。方法采用小鼠急性经口毒性试验并采用霍恩法测定半数致死量(LD50)。结果 1周内试验动物未见明显中毒症状及死亡发生,采用霍恩法测定LD50>10g/kg。结论基因重组Kringle 5蛋白属实际无毒级。     

Acute oral toxicity test and assessment of rhynchophylline in mice

As the main alkaloid constituent of Uncaria species, rhynchophylline has drawn extensive attention in recent years for its antihypertensive and neuroprotective activities. However, toxicity study of the rhynchophylline is still lacking. In the present study, oral acute toxicity of rhynchophylline was conducted in Kunming mice. The mice were orally treated with 520.00, 442.00, 375.70, 319.34 and 271.44 mg/kg of rhynchophylline for 14 d. The general behavior, body weight changes, toxic reaction, and death were recorded, and histopathological analyses were performed. The acute toxicity was evaluated by the assessment of the median lethal dose (LD₅₀). The acute toxicity study showed that no significant difference was found in the body weight of the mice in the control group and those in the drug group. However, the mice treated with rhynchophylline showed obvious abnormal symptoms and mortality. The median lethal dose (LD₅₀) of orally administered rhynchophylline was 308.08 mg/kg. The histopathological results showed that the mice in the high-dose rhynchophylline group displayed toxic effects in the brain, liver, lung, and kidney. The results of the current study indicated that rhynchophylline could not be taken at a high dose. Collectively, our current findings provided a strong basis for further clinical investigation.     

Acute toxicity of berberine and its correlation with the blood concentration in mice

The aim of this study was to investigate the LD₅₀ (median lethal dosage) of berberine (BBR) through three different routes of injection in mice: intravenous (IV) injection, intraperitoneal (IP) injection, and intragastric (IG) oral administration. The concentration of BBR in blood from their IG doses (10.4, 20.8, 41.6, and 83.2 g/kg) and the content relationship of BBR among different injections were analyzed by high-performance liquid chromatography (HPLC). The LD₅₀ of BBR from IV and IP injections is 9.0386 and 57.6103 mg/kg, respectively; but no LD₅₀ was found in the IG group. A significant difference in bioavailability was observed between the different routes. Furthermore, the concentration of BBR in the blood from different IG doses was also significantly different. However, we discovered an interesting phenomenon indicating that the absorption of BBR by oral administration has a limit, therefore, explaining the difficulty in obtaining an LD₅₀ of BBR for IG injection. From the analysis of BBR content in blood after various administrations, we hypothesized that not only does the concentration of BBR in blood contribute to its acute toxicity, but also the routes of administration may be an important facet that affects this toxicity evaluation.     

Acute and a 28-day repeated-dose toxicity study of total flavonoids from Clinopodium chinense (Benth.) O. Ktze in mice and rats

Clinopodium chinense (Benth.) O. Ktze (Labiatae), known as ‘Duanxueliu’ in the Chinese Pharmacopoeia, has been widely used as a traditional Chinese medicine for the treatment of hemorrhagic disease. Total flavonoids from Clinopodium chinense (Benth.) O. Ktze (TFCC), the most active ingredient, possess a variety of properties, such as antioxygenation. Until now, evidence-based toxicity data on TFCC has been limited. This study evaluated the acute (in mice and rat) and the 28-day repeated-dose (in rat) toxicity study of TFCC, respectively. In acute study, oral administration of TFCC to rats and mice did not induce toxicity or mortality up to the maximum doses of 4000 and 5000 mg/kg, respectively. In subacute toxicity study, we administered TFCC at daily doses of 70, 210, and 630 mg/kg for 4 consecutive weeks to rats via gavage. We observed no changes in food consumption, water intake, body weight, chemistry and hematological parameters, organ weight, gross pathology or histopathology. No animals from any group died. These findings indicate that TFCC is relatively nontoxic, and provide practical guidance for selecting a safe dose for further investigation of TFCC in animal studies or clinical trials.     

Oral and intraperitoneal acute toxicity studies of yessotoxin and homoyessotoxins in mice.

The acute toxicity of yessotoxin (YTX), homoyessotoxin (homoYTX) and 45-hydroxy-homoyessotoxin (45-OH-homoYTX) has been studied in comparison to that of okadaic acid (OA), the main diarrhogenic toxin, both after intraperitoneal (i.p.) and oral administration. After i.p. administration, homoYTX and YTX showed similar lethality (LD(50)=444 microg/kg and 512 microg/kg), higher than that of OA (LD(50)=225 microg/kg), while 750 microg/kg of 45-OH-homoYTX did not cause death. OA induced the already known toxic signs: before death, mice were motionless and cyanotic; small intestine and liver damage were shown at post-mortem. Mice treated with YTX and homoYTX were restless and jumped before death; necroscopy did not show major changes. After oral treatment, 2 mg/kg of OA induced diarrhoea and body weight loss, causing 4/5 deaths; necroscopy and/or histology revealed degenerative lesions to small intestine, forestomach and liver (confirmed by increased plasma transaminase), but no myocardium alterations. On the contrary, the oral treatment with YTX (1 and 2 mg/kg) and its derivatives (1 mg/kg) did not cause any death or signs of toxicity, except some ultrastructural myocardiocyte alterations, adjacent to capillaries, such as cytoplasmic protrusions (YTX, 1 and 2 mg/kg), fibrillar alteration (YTX, 1 mg/kg) or mitochondria assemblage (45-OH-homoYTX). Altogether, our data show that YTX and its derivatives are less toxic than OA after acute oral and i.p. treatments, at doses which may represent up to 100 times of the possible human daily intake.