CN105434452A - 一种犬用复方甲替沙星注射液的制备工艺 - Google Patents
一种犬用复方甲替沙星注射液的制备工艺 Download PDFInfo
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Abstract
一种犬用复方甲替沙星注射液的制备工艺，甲替沙星加入到注射用水中，加入酸性助溶剂、非水溶剂，于加热条件下搅拌至溶解，再依次加入盐酸氨溴索、阿奇霉素继续搅拌至溶解，得到A溶液，另取注射用水，依次加入亚硫酸氢钠，EDTA-2NA，搅拌得到B溶液，把B溶液加入A溶液，搅匀，待药液澄明后，调节PH值，再加入注射用水制得成品；酸性助溶剂的使用提高了阿奇霉素与甲替沙星的溶解度，非水溶媒的使用提高了阿奇霉素与甲替沙星的稳定性，并能延缓药物吸收，临床无需现配其它抗菌药物或祛痰药物，具有使用方便，给药次数少，使用效果好的特点。
Description
技术领域
本发明涉及兽药技术领域的药物，具体说来涉及一种犬用复方甲替沙星注射液的制备工艺。
背景技术
甲替沙星属于第四代氟喹诺酮类新型化学合成抑菌剂，为淡黄色结晶性粉沫，味苦，不溶于水，易溶于碱性溶液，为第四代氟喹诺酮类广谱杀菌药，其抗菌作用是通过抑制细菌的DNA旋转酶和拓扑异构酶IV，从而抑制细菌DNA复制、转录和修复过程。体外试验表明，其对革兰氏阳性菌中的金黄色葡萄球菌(仅限于对甲氧西林敏感的菌株)、链球菌，革兰氏阴性菌中的大肠杆菌、流感和副流感嗜血杆菌、肺炎克雷伯杆菌、卡他莫拉菌、沙门氏菌、异变形杆菌、绿脓杆菌、嗜血杆菌、多杀性巴氏杆菌、溶血性巴氏杆菌、肺炎衣原体、嗜肺性军团杆菌、肺炎支原体等均有抑制杀灭作用。甲替沙星抗革兰阳性菌和阴性菌活性为环丙沙星和左氧氟沙星的2～32倍，对耐青霉素和大环酯类药物的肺炎链球菌有效；对已发生基因突变的环丙沙星、恩诺沙星耐药革兰氏阳性菌株，甲替沙星的杀菌作用为环丙沙星、恩诺沙星的4倍以上。甲替沙星抗衣原体的作用是左氧氟沙星的4倍，环丙沙星的16倍。
甲替沙星注射剂和口服剂有生物等效性，该药易吸收，且不受饮食因素影响，达峰时间短(服用1～2小时后达峰)，半衰期约7～14小时，绝对生物利用度高。血浆蛋白结合率低，在体内分布广，组织穿透力强，能广泛地分布在许多组织和液体中，在靶组织中的浓度较血清高。甲替沙星在体内代谢极低，大部分以原形经肾脏从尿中排出。
Ames试验中甲替沙星对多种菌株无致突变作用，对胎鼠有明显的致畸胎作用。甲替沙星对包括犬在内的实验动物有很高的安全性。
由于该药优良的广谱抗菌抗支原体作用和药物动力学特点及很高的安全性，现已广泛用于人的呼吸道、消化道感染、泌尿生殖感染及皮肤软组织感染，国内犬用抗菌药品种极少，仅有复方阿莫西林注射液等有限几个品种，且依赖进口，而该药在犬细菌、支原体感染治疗中有应用潜力。但该药味极苦，内服给药对味觉发达的犬来说适口性很差，容易产生厌食现象，影响该药的使用。犬临床上混合感染普遍，对混合感染仍需联合用药；该药只有抗菌、抗支原体对因治疗作用，见效相对慢。
目前，甲替沙星注射剂的专利及已上市的有甲替沙星注射液、盐酸甲替沙星注射液、甲磺酸甲替沙星注射液等，均供静脉滴注，不适合皮下注射使用。
鉴于上述原因，现研发出一种犬用复方甲替沙星注射液的制备工艺。
发明内容
本发明的目的是为了克服现有技术中的不足，提供一种犬用复方甲替沙星注射液的制备工艺，本产品对细菌、支原体感染引起的呼吸道炎症有标本兼治的作用，酸性助溶剂的使用提高了阿奇霉素与甲替沙星的溶解度，非水溶媒的使用提高了阿奇霉素与甲替沙星的稳定性，并能延缓药物吸收，临床无需现配其它抗菌药物或祛痰药物，具有使用方便，给药次数少，使用效果好的特点。
本发明为了实现上述目的，采用如下技术方案：一种犬用复方甲替沙星注射液的制备工艺，所述犬用复方甲替沙星注射液由以下组分制备组成：甲替沙星3～10g，阿奇霉素0.75～2.5g，盐酸氨溴索0.10～0.5g，酸性助溶剂3～12ml，非水溶剂10～40ml，亚硫酸氢钠0.2g，EDTA-2NA0.02g，以上各组分加入注射用水后总量为100ml。
甲替沙星与阿奇霉素重量比为2～4∶1，甲替沙星与盐酸氨溴索重量比为10～40∶1。
所述的酸性助溶剂为盐酸、醋酸、乳酸、硫酸，其中一种或几种的组合。
所述的非水溶剂为乙醇、丙二醇、α-吡咯烷酮、聚乙二醇400、二甲基甲酰胺、苯甲醇，其中一种或几种的组合。
第一步，称取甲替沙星加入到20～50ml注射用水中，依次加入酸性助溶剂、非水溶剂，于50～90℃加热条件下搅拌至溶解，再依次加入盐酸氨溴索、阿奇霉素继续搅拌至溶解，得到A溶液，备用；
第二步，另取注射用水5ml，依次加入亚硫酸氢钠0.2g，EDTA-2NA0.02g，搅拌至完全溶解，得到B溶液，备用；
第三步，再把B溶液以边加边搅拌的方式加入A溶液，搅匀后，保持10～20分钟，待药液澄明后，调节PH值为3.0～4.5，再加入注射用水后总量为100ml，制得成品。
本发明的有益效果是：阿奇霉素为大环内酯类广谱抗生素，对革兰氏阳性菌、某些阴性菌、支原体及弓形体均有作用。阿奇霉素与甲替沙星做成复方后合用，可拓宽抗病原体范围，增强抗菌抗支原体效果，减少临床用药现配麻烦；盐酸氨溴索为强力祛痰药物，能迅速改善呼吸道症状，故甲替沙星与阿奇霉素、盐酸氨溴索联合制成复方注射液，对细菌、支原体感染引起的呼吸道炎症有标本兼治的作用。酸性助溶剂的使用提高了阿奇霉素与甲替沙星的溶解度，非水溶媒的使用提高了阿奇霉素与甲替沙星的稳定性，并能延缓药物吸收。
本发明通过皮下或肌肉注射给药，临床无需现配其它抗菌药物或祛痰药物，具有使用方便，给药次数少，使用效果好的特点。
具体实施方式
下面结合实施例与具体实施方式对本发明作进一步详细说明：
实施例1
第一步，称取甲替沙星5g加入到40ml注射用水中，依次加入乳酸6ml、丙二醇35ml，于70℃加热条件下搅拌至溶解，再依次加入盐酸氨溴索0.2g、阿奇霉素1.5g继续搅拌至溶解，得到A溶液，备用；
第二步，另取注射用水5ml，依次加入亚硫酸氢钠0.2g，EDTA-2NA0.02g，搅拌至完全溶解，得到B溶液，备用；
第三步，再把B溶液以边加边搅拌的方式加入A溶液，搅匀后，保持15分钟，待药液澄明后，调节PH值为3.7，再加入注射用水后总量为100ml，制得成品。
实施例2
第一步，称取甲替沙星4g加入到40ml注射用水中，依次加入乳酸与醋酸共5ml、丙二醇30ml，于65℃加热条件下搅拌至溶解，再依次加入盐酸氨溴索0.15g、阿奇霉素1.25g继续搅拌至溶解，得到A溶液，备用；
第二步，另取注射用水10ml，依次加入亚硫酸氢钠0.2g，EDTA-2NA0.02g，搅拌至完全溶解，得到B溶液，备用；
第三步，再把B溶液以边加边搅拌的方式加入A溶液，搅匀后，保持13分钟，待药液澄明后，调节PH值为4.2，再加入注射用水后总量为100ml，制得成品。
Claims (5)
1.一种犬用复方甲替沙星注射液，其特征在于：由以下组分制备组成：甲替沙星3～10g，阿奇霉素0.75～2.5g，盐酸氨溴索0.10～0.5g，酸性助溶剂3～12ml，非水溶剂10～40ml，亚硫酸氢钠0.2g，EDTA-2NA0.02g，以上各组分加入注射用水后总量为100ml。
2.根据权利要求1所述的一种犬用复方甲替沙星注射液，其特征在于：甲替沙星与阿奇霉素重量比为2～4∶1，甲替沙星与盐酸氨溴索重量比为10～40∶1。
3.根据权利要求1所述的一种犬用复方甲替沙星注射液，其特征在于：所述的酸性助溶剂为盐酸、醋酸、乳酸、硫酸，其中一种或几种的组合。
4.根据权利要求1所述的一种犬用复方甲替沙星注射液，其特征在于：所述的非水溶剂为乙醇、丙二醇、α-吡咯烷酮、聚乙二醇400、二甲基甲酰胺、苯甲醇，其中一种或几种的组合。
5.一种犬用复方甲替沙星注射液的制备工艺，其特征在于：
第一步，称取甲替沙星加入到20～50ml注射用水中，依次加入酸性助溶剂、非水溶剂，于50～90℃加热条件下搅拌至溶解，再依次加入盐酸氨溴索、阿奇霉素继续搅拌至溶解，得到A溶液，备用；
第二步，另取注射用水5ml，依次加入亚硫酸氢钠0.2g，EDTA-2NA0.02g，搅拌至完全溶解，得到B溶液，备用；
第三步，再把B溶液以边加边搅拌的方式加入A溶液，搅匀后，保持10～20分钟，待药液澄明后，调节PH值为3.0～4.5，再加入注射用水后总量为100ml，制得成品。
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