CN108392469A - 硫普罗宁在制备抗柔嫩艾美耳球虫药物中的应用 - Google Patents
硫普罗宁在制备抗柔嫩艾美耳球虫药物中的应用 Download PDFInfo
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- tiopronin
- eimeria tenella
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- NIUFFODHMKLSCH-UHFFFAOYSA-N sodium;(4-aminophenyl)sulfonyl-(6-chloropyrazin-2-yl)azanide Chemical compound [Na+].C1=CC(N)=CC=C1S(=O)(=O)[N-]C1=CN=CC(Cl)=N1 NIUFFODHMKLSCH-UHFFFAOYSA-N 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
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- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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Abstract
本发明公开了硫普罗宁在制备抗柔嫩艾美耳球虫药物中的应用，其中，该抗柔嫩艾美耳球虫药物为散剂或水溶性粉剂。本发明的有益之处在于：通过动物感染实验证实，硫普罗宁的抗球虫指数(ACI)可达到175以上，具有较好的抗柔嫩艾美耳球虫作用，是预防和治疗柔嫩艾美耳球虫病理想的有效药物。
Description
技术领域
本发明涉及一种化合物的新应用，具体涉及硫普罗宁在制备抗柔嫩艾美耳球虫药物中的应用，属于化学技术领域。
背景技术
鸡球虫病是严重危害集约化养鸡业生产的最主要疫病，每年因此而造成的经济损失高达25亿英镑以上，其病原是顶复门原虫类的艾美耳球虫(Eimeria spp)，其中危害最大的是柔嫩艾美耳球虫(Eimeria tenella)。我国对此虽然至今无准确统计，但最保守的估计其损失应不小于25亿元RMB。化学药物治疗是控制鸡球虫病的重要措施之一，但目前鸡球虫具有广泛而严重的抗药性，迫切需要新的抗球虫药物面市。
硫普罗宁，英文名称：Tiopronin，分子式是C5H9NO3S，分子量163.19，CAS登录号：1953-02-2，化学结构如下：
硫普罗宁是一种与青霉胺性质相似的含巯基药物，具有保护肝脏组织及细胞的作用。动物试验表明，硫普罗宁保护肝脏组织和细胞的作用机制为：
1、硫普罗宁能够防止四氯化碳、乙硫氨酸、毒蕈粉及扑热息痛对肝脏的损害，并可预防由于四氯化碳而导致的肝坏死，可加快乙醇和乙醛的降解、排泄，防止甘油三酯的堆积，对酒精性肝损伤有显著修复作用。
2、硫普罗宁可使肝细胞线粒体中的ATPase活性降低，ATP含量升高，电子传递功能恢复正常，从而改善肝细胞功能，对抗各类肝损伤负效应。
3、硫普罗宁可促进肝细胞再生，表现为乳酸脱氢酶活性、苹果酸酶活性、DNA含量及肝总蛋白含量均升高。
4、硫普罗宁结构中含有巯基，能与自由基可逆性结合成二硫化物，作为一种自由基清除剂，还可激活铜、锌、SOD酶以增强其清除自由基的作用。
硫普罗宁在临床上主要用于治疗急、慢性肝炎、肝硬化、酒精性肝损伤和药物引起的肝损伤，也用于金属中毒、化疗及放疗保护、荨麻疹、皮炎、湿疹和痤疮等，还用于初期老年白内障。
截至目前，尚没有有关硫普罗宁具有抗柔嫩艾美耳球虫作用的报道，并且通过硫普罗宁已知的性质无法推断其是否具有抗柔嫩艾美耳球虫的作用。
发明内容
本发明的目的在于提供硫普罗宁在制备抗柔嫩艾美耳球虫药物中的新应用。
为了实现上述目标，本发明采用如下的技术方案：
1、硫普罗宁在制备抗柔嫩艾美耳球虫药物中的应用，其特征在于，所述抗柔嫩艾美耳球虫药物的制备方法为：将硫普罗宁与可接受的辅料混合，制成散剂。
2、硫普罗宁在制备抗柔嫩艾美耳球虫药物中的应用，其特征在于，所述抗柔嫩艾美耳球虫药物的制备方法为：将硫普罗宁与可接受的辅料混合，制成水溶性粉剂。
本发明的有益之处在于：通过动物感染试验证实，硫普罗宁的抗球虫指数(ACI)可达到175以上，具有较好的抗柔嫩艾美耳球虫作用，是预防和治疗柔嫩艾美耳球虫病理想的有效药物。
具体实施方式
以下结合具体实施例对本发明作具体的介绍。
一、制备硫普罗宁散剂
取5g硫普罗宁(含量不低于99％)和95g淀粉，混匀，制成散剂。
二、制备硫普罗宁水溶性粉剂
取2.5g硫普罗宁(含量不低于99％)和97.5g葡萄糖，混匀，制成水溶性粉剂。
三、散剂、水溶性粉剂的用法用量
1、散剂的用法用量
将上述100g散剂拌入100kg饲料中(每100kg饲料中含有5g硫普罗宁)，按日常食量喂食。
2、水溶性粉剂的用法用量
将上述100g水溶性粉剂溶于100L水中(每100L水中含有2.5g硫普罗宁)，在用药前给试验鸡断水2h，然后按正常饮水量喂食。
四、抗柔嫩艾美耳球虫试验
1、试验材料
对照药物：三字球虫粉(30％磺胺氯吡嗪钠，由上海诺华动物保健有限公司生产，批号001010)。
试验药物1：硫普罗宁散剂。
试验药物2：硫普罗宁水溶性粉剂。
球虫卵囊：柔嫩艾美耳球虫(Eimeria tenella)广东株孢子化卵囊，由广东省农业科学院兽医研究所保存，使用前在无球虫雏鸡体内复壮。
雏鸡：岭南黄雏鸡，由广东省农业科学院畜牧研究所提供，饲养于已消毒的专用动物房内；鸡笼和所用器皿均严格消毒，自由采食和饮用纯净水；试验前观察雏鸡有无临床症状及连续2d检查粪便有无球虫卵囊，备用。
饲料：由广东省新南都饲料有限公司定制育雏料，不含任何抗球虫药物。
2、试验方法
分组：按试验分组及处理将150只岭南黄雏鸡饲养至10日龄，逐只称重，淘汰弱雏和体重过大者，将剩余雏鸡随机分成5组，每组30只，并适当调整使每组雏鸡总体重大致相等。
处理：除第I组(空白对照组)外，其余各组雏鸡均经口灌服柔嫩艾美耳球虫孢子化卵囊l×105个/羽；除第I组和第Ⅱ组(阳性对照组)外，其余各组雏鸡均于感染后立即饲喂或饮用含抗球虫药物的饲料或水，第Ⅲ组饲喂含三字球虫粉的饲料，第Ⅳ组饲喂硫普罗宁散剂与饲料制成的硫普罗宁拌料，第Ⅴ组饮用硫普罗宁水溶性粉剂与饮水制成的硫普罗宁饮水，各组饮水和饲料的用量均相同。试验雏鸡的分组情况见表1。
表1试验雏鸡分组
每天观察并记录鸡群的精神状况、采食量、粪便情况等；对死亡雏鸡称重，剖检，若为柔嫩艾美耳球虫感染引起死亡则病变记分为+4分；所有雏鸡于感染后第7d逐只称重，剖检，进行盲肠病变记分；最后计算各组雏鸡的增重和饲料报酬。
药效判定方法及标准抗球虫指数(ACI)按美国默克公司推荐的公式计算：
ACI＝(相对增重率+存活率)－(卵囊值+病变值)；
相对增重率＝(试验组增重÷空白对照组增重)×100％；
存活率＝(各组存活雏鸡数÷各组雏鸡总数)×100％。
病变按五级记分：
(1)无卵囊，盲肠正常，记为0分；
(2)有卵囊，盲肠黏膜稍增厚，有少量散在出血或少量血样肠内容物，记为+1分；
(3)有卵囊，盲肠黏膜增厚，有明显出血或明显血样肠内容物，记为+2分；
(4)有卵囊，盲肠黏膜增厚，有大量凝血块或血样肠芯，记为+3分；
(5)雏鸡因球虫病死亡或有大量卵囊，盲肠外观呈酱油色(或小肠中部有点状坏死灶，黏膜面呈绯红色)，肠管明显肿大，内容物形成明显的血样肠芯，记为+4分。
组内病变值＝每组平均病变记分×20。
药效判定标准是：ACI<120为无效，120～160为弱效，160～180为中效，180以上为强效。
卵囊值由盲肠内容物克卵囊数(OPG)换算而来。
3、试验结果
临床症状观察：接种柔嫩艾美耳球虫孢子化卵囊的对照组第2d，雏鸡出现精神沉郁，呆立，食欲减退；第5d出现明显血便，并出现死亡，随后血便逐渐减少。
分别计算各组的抗球虫指数，计算结果见表2。
表2各组抗球虫指数
由表2可知：
1、第Ⅲ组、第Ⅳ组、第Ⅴ组的抗球虫指数均高于第Ⅱ组；
2、第Ⅳ组、第Ⅴ组的抗球虫指数明显高于第Ⅲ组。
通过上述试验以及试验结果我们可以获知：硫普罗宁的抗球虫指数(ACI)可达到175以上，具有较好的抗柔嫩艾美耳球虫的作用，且明显优于常规抗球虫药物三字球虫粉，是预防和治疗柔嫩艾美耳球虫病理想的有效药物。
需要说明的是，上述实施例不以任何形式限制本发明，凡采用等同替换或等效变换的方式所获得的技术方案，均落在本发明的保护范围内。
Claims (7)
1.硫普罗宁在制备抗柔嫩艾美耳球虫药物中的应用。
2.根据权利要求1所述的应用，其特征在于，所述抗柔嫩艾美耳球虫药物的制备方法为：将硫普罗宁与可接受的辅料混合，制成散剂。
3.根据权利要求2所述的应用，其特征在于，所述可接受的辅料为淀粉。
4.根据权利要求3所述的应用，其特征在于，所述硫普罗宁与淀粉的用量比为5g：95g。
5.根据权利要求1所述的应用，其特征在于，所述抗柔嫩艾美耳球虫药物的制备方法为：将硫普罗宁与可接受的辅料混合，制成水溶性粉剂。
6.根据权利要求5所述的应用，其特征在于，所述可接受的辅料为葡萄糖。
7.根据权利要求6所述的应用，其特征在于，所述硫普罗宁与葡萄糖的用量比为2.5g：97.5g。
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