Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

氯硝柳胺乙醇胺盐可湿性粉剂杀螺效果实验观察

安徽省淮南市第三制药厂生产的氯硝柳胺乙醇胺盐50％可湿性粉剂,经实验室浸杀法及现场喷洒法灭螺实验,证明该药使用方便、作用迅速、杀螺力强。该药2g/m~2喷洒法与五氯酚钠10g/m~2比较,3～15d杀螺效果相仿,30d杀螺效果比五氯酚钠高,浸杀法灭螺,钉螺上爬较少。     

萃取光度法测定水中氯硝柳胺含量的研究

目的实验室条件下,采用萃取光度法测定水中氯硝柳胺含量。方法采用1:9乙酸丁酯-石油醚混合溶剂萃取,再用NaOH反萃取有机相中的氯硝柳胺,用双波长光度法测定。结果在实验室条件下,氯硝柳胺的提取率达93％。测定的线性范围为0-4g／m3,检出限为0．042 7 g／m3, 方法的表观摩尔吸光系数为1．26×105L／(mol·cm)。结论萃取光度法能用于水样中氯硝柳胺含量的现场检测。     

丹阳市不同环境药物灭螺效果

目的 目的 评价在有螺江滩、 河道、 渠道连续使用氯硝柳胺乙醇胺盐后的灭螺效果。方法 方法 选择丹阳市后巷镇北魏 江滩、 陵口镇肖梁河、 云阳镇老庙渠道作为研究现场, 采用4%氯硝柳胺乙醇胺盐粉剂50 g/m2 和26%四聚杀螺胺 （2～4） g/m2 实施灭螺。综合利用历史资料和现场调查资料, 评价连续应用灭螺药物后的效果。结果 结果 至2013年, 北魏江滩、 肖梁河、 老庙渠道钉螺面积较首次复现时分别下降了82.80%、 63.14%和70.00%, 钉螺面积与钉螺密度均呈显著正相关 （r = 0.931、 0.975、 0.916, P均＜0.05）; 灭螺后活螺平均密度较首次复现时下降了92.34%、 87.91%和97.66%。灭螺后钉螺校正死亡率 与次年活螺平均密度均呈负相关（r = -0.998、 -0.999、 -0.970）; 活螺密度下降率与次年活螺平均密度均呈负相关 （r = -0.997、 -0.998、 -0.868）。结论 结论 药物灭螺在压缩钉螺面积、 降低钉螺密度、 控制血吸虫病传播等方面效果明显。     

4％杀螺胺乙醇胺盐粉剂在沟渠环境的灭螺效果观察

目的 评价4％杀螺胺乙醇胺盐粉剂在沟渠环境的灭螺效果,为现场扩大应用提供科学依据. 方法 选择湖北省江陵县马家寨乡有钉螺孳生的5条垸内沟渠,随机选择其中2条沟渠为4％杀螺胺乙醇胺盐（niclosamide ethanolamine powder,4％NEP）试验组,2条分别为26％四聚·杀螺胺悬浮液（sus-pension concentrate of 26％ metaldehyde and niclosamide,26％SCMN）和50％氯硝柳胺乙醇胺盐可湿性粉剂（wetable powder of 50％ niclosamide ethanolamine salt,50％WPNES）对照组,1条为空白对照组.分别采用25、50 g/m2两种剂量的4％NEP剂进行喷粉法灭螺,与26％SCMN、50％WPNES喷洒灭螺效果进行比较.施药前及施药1、3、7d后,采用系统抽样法对5条沟渠按框距10 m设框进行钉螺调查,检测所有拣获钉螺,统计钉螺数量和死亡数.采用SPSS 17.0软件对施药后的钉螺死亡率进行统计学分析.分析不同药物的灭螺费用. 结果 施药后,各组钉螺死亡率均逐渐上升,25、50 g/m2两种剂量的4％NEP组施药1、3、7 d后钉螺死亡率依次为73.68％（336/456）、81.84％ （383/468）、80.75％（344/426）和74.76％（391/523）、85.86％ （425/495）、82.99％ （366/441）;26％SCMN组施药1、3、7d后的钉螺死亡率依次为70.77％ （351/496）、80.59％ （353/438）、82.01％ （319/389）;50％WPNES组施药1、3、7d后的钉螺死亡率依次为69.95％（291/416）、81.35％（314/386）、75.61％ （248/328）.经统计学分析,施药后1d,4％NEP 25 g/m2组、4％NEP50 g/m2组分别与50％ WPNES和26％ SCMN组比较,钉螺死亡率差异无统计学意义（x2分别为0.t48,1.500,1.007,2.696,2.052,P均＞0.05）;施药后3d,4％NEP 50 g/m2组与26％SCMN组比较,钉螺死亡率间差异有统计学意义（x2=4.650,P＜0.05）;4％NEP 25 g/m2组分别与4％NEP 50 g/m2组、50％WPNES组和26％SCMN组比较,钉螺死亡率间差异无统计学意义（x2=2.880,0.034,0.230,P均＞0.05）;4％ NEP50 g/m2组与50％WPNES组比较,钉螺死亡率差异无统计学意义（x2=3.265,P＞ 0.05）.施药后7d,4％NEP 50 g/m2组与50％WPNES组比较,钉螺死亡率差异有统计学意义（x2=6.372,P＜ 0.05）;4％NEP 25 g/m2 组分别与4％NEP 50 g/m2组、50％WPNES组和26％SCMN组比较,钉螺死亡率间差异无统计学意义（x2分别为0.734,2.904,0.211;P均＞0.05）;4％NEP 50 g/m2组与26％SCMN组比较,钉螺死亡率间差异无统计学意义（x2=1.140,P＞ 0.05）.灭螺效果均优于对照组.4％NEP 25 g/m2、50 g/m2组灭螺费用分别为16.31元/100 m2、27.28元/100 m2;26％SCMN组费用为30.84元/100 m2;50％WPNES组费用为32.24元/100 m2. 结论 4％杀螺胺乙醇胺盐粉剂可在缺少充足水源的沟渠环境实施灭螺,效果较好且较为便宜.     

钉螺对氯硝柳胺抗药性的实验研究

目的研究氯硝柳胺在现场长期使用后,钉螺对其产生抗药的可能性。方法捕捉安徽省铜陵县胥坝乡长期使用氯硝柳胺进行灭螺地区的钉螺作为实验螺,以该乡未使用过氯硝柳胺灭螺地区的钉螺作为对照螺。将氯硝柳胺用脱氯自来水配成有效浓度为2.0000、1.0000、0.5000、0.2500、0.1250、0.0625和0.0313mg/L的药液,在(24±1)℃下对实验和对照钉螺进行室内浸杀试验,观察钉螺死亡情况,计算半数致死浓度(LC50)等指标。结果浸杀24、72和120h后,实验组钉螺LC50分别为0.337、0.175和0.136mg/L,对照组钉螺的LC50分别为0.165、0.090和0.061mg/L;氯硝柳胺浓度为0.0625～0.0250mg/L时,实验组钉螺的死亡率均显著低于对照组。结论氯硝柳胺在现场长期使用后,钉螺可能对其产生抗药性。     

Niclosamide Modulates the Cellular and Humoral Immune Response in Balb/c Mice

Background: Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses. Objective: This study aimed to evaluate the impact of niclosamide on immune response of mice. Methods: Niclosamide was administered to balb/c mice. To evaluate cell-mediated immune response, a contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test were performed, whereas a humoral immune response was evaluated by hemagglutination assay (HA) and mice lethality test. The concentration of TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) on murine peritoneal macrophages. Results: In the CHS test, niclosamide caused a decrease in skin thickness, significantly exhibiting a decrease in inflammation. A highly significant decrease in overall leukocyte count (lymphocytes and neutrophils) was observed before and after cyclophosphamide injection as compared with the control group. However, only a highly significant decrease in the neutrophil percentage was observed. Niclosamide has decreased the phagocytic process immensely compared with the control. In the HA titer, niclosamide was found to reduce the antibodies' titer compared with the negative control group. In the mice lethality test, the treatment groups have shown an increase in the percentage of mortality. TGF-β1 elevated in peritoneal macrophages when treated with niclosamide, in a dose-dependent manner. Conclusion: Niclosamide exerts potent immunomodulatory effects by significantly suppressing cell-mediated and humoral immune responses and increasing the levels of TGF-β1 in mice. Niclosamide might be added as an adjuvant to immunosuppressive drugs for the treatment of autoimmune diseases.     

杀螺剂室内筛选实验方法标准化的研究Ⅰ.药液体积对杀螺效果的影响

目的 了解杀螺剂的不同药液体积对杀螺效果的影响。方法 实验室25℃浸泡杀螺。结果 每只钉螺用药液体积分别为0．5、1．0、2．0、3．3、10．0和20．0ml浸杀时，24h的LC50值分别为0．2242、0．1768、0．1064、0．0788、0．0788和0．0654mg/L，随药液体积增加杀螺效果增加，但增加至3.3ml/只后杀螺效果基本一致；48h的LC50值分别为0．0670、0．01167、0．0754、0．0640、0．0611和0．0367mg/L,1.0ml／只以上药液体积杀螺效果与24h组杀螺效果基本一致，但0．5ml/只组杀螺效果反而高于较大药液体积组。结论 实验室浸泡每只钉螺的杀螺药液体积宜大于3.3ml。     

氯硝柳胺对鼠伤寒沙门氏菌致突变试验

本文采用鼠伤寒沙门氏菌诱变性试验（Ａｍｅｓ试验）．对新型长效杀螺剂－氯硝柳胺控释剂主药氯硝柳胺进行了致突变作用的研究。在最小抑菌剂量４０μｇ／Ⅲ以下０．１２５－８μｇ／Ⅲ范围内，实验证明无致突变作用。     

氯硝柳胺控释剂药物动力学的研究

通过对氯硝柳胺控释剂这一双层(速释层和缓释层)包衣丸剂药物动力学的研究,观察到其降解过程是按一级反应进行,并得出有关药物动力学参数,该控释剂半减期长,具有缓慢释药的长效作用。现场施药及室内流水冲洗1年、1.5年后,该制剂尚剩余药量7.62％和19.5％,其浸液仍有灭螺效果;远比常规氯硝柳胺糊剂喷洒法的理论持效时间长(9.7d),理论用药量少。不仅避免药物浪费,而且减轻环境污染和对鱼类的毒害等。结果提示:氯硝柳胺控释剂是一个研制成功的新型长效杀螺剂。