盐酸沃尼妙林制剂的制备及抗菌效果研究

发布时间：2019-03-26 15:32

【摘要】：盐酸沃尼妙林(VAlnemulin,缩写为：VA)为新一代半合成类动物专用抗生素,属于二萜烯类。在兽医临床上国外主要用于预防和治疗由革兰氏阳性菌及支原体引起的各种动物疾病。具有抗菌谱广、抗菌活性相对较强,半衰期短、首过效应显著、血浆浓度受给药方法影响等特点。本文制备了VA透皮软膏剂、甘油明胶栓及颗粒剂,并且对其抗菌效果进行了研究。 1.甘油明胶栓的制备及其对阴道炎效果的研究 1.1甘油明胶栓的制备水溶性基质PEG类、甘油明胶类；油脂性基质主要是半合成脂肪酸甘油酯为基质,采用热熔法,以栓剂的溶出度、融变时限为考察指标筛选基质的种类与用量。结果显示：用热熔法制备的甘油明胶栓性质稳定。 1.2甘油明胶栓的质量评价参照《中国兽药典》(2010版)对制备的栓剂进行外观、重量差异、融变时限及溶出度检查,结果可知,各项均符合《中国兽药典》(2010版)要求,且质量稳定。 1.3甘油明胶栓对细菌性阴道炎治疗效果研究对大鼠分别采用单次及多次阴道给药,进行刺激性试验,并用金黄色葡萄球菌感染大鼠的阴道,再用VA栓治疗,并评价其药效。结果表明,该制剂对大鼠的阴道无刺激性；VA栓低、中、高(50、100、150mg·Kg-1)剂量阴道给药对金黄色葡萄球菌的总的转阴率分别为60%、100%、100%,VA栓中、高剂量与奥硝唑栓(100mg·Kg-1)疗效相当,无显著性差异(P0.05)。 2.软膏剂的制备及抗菌效果研究采用乳化法分别制备W/O型和O/W型VA软膏剂,并用高效液相色谱法测定软膏剂中VA的体外透皮释药率。结果表明,W/O型、O/W型软膏剂10h的体外透皮释药率分别为30%±0.42%、18.45%±0.69%。体外抑菌实验表明,W/O型对金黄色葡萄球菌的抑制作用更显著,制备的两种软膏剂稳定性均良好。 3.颗粒剂的制备及其对大肠杆菌性腹泻治疗效果研究 3.1颗粒剂的制备工艺优化采用湿法制粒制备VA颗粒剂,以颗粒剂的成型性、吸湿率和溶化性为考察指标,筛选辅料的种类及用量。结果表明,制备的颗粒剂质量符合《中国兽药典》(2010版)要求,筛选出的最优处方工艺合理可行。 3.2颗粒剂的质量评价采用湿法制粒制备VA颗粒剂,利用紫外分光光度法测定颗粒剂中VA的含量,结果显示,用UV测定颗粒剂中VA的含量,方法较简便可靠,重现性好。外观性状、粒度、干燥失重、溶化性等均符合《中国兽药典》(2010版)要求。 3.3颗粒剂对大肠杆菌性腹泻治疗效果试验以小鼠为实验动物,用致病性大肠杆菌经腹腔注射感染小鼠建立腹泻模型,4h后给予不同剂量的VA颗粒剂灌胃治疗。治疗3d后,结果显示,VA颗粒剂对大肠杆菌性腹泻的治疗效果显著。
[Abstract]:VAlnemulin, (: VA) for short) is a new generation of semi-synthetic antibiotics for animals, belonging to diterpene. In veterinary clinic, it is mainly used to prevent and treat all kinds of animal diseases caused by gram-positive bacteria and mycoplasma. It has broad antibacterial spectrum, relatively strong antibacterial activity, short half-life, remarkable first-pass effect, and the plasma concentration is affected by the method of administration. In this paper, VA transdermal ointment, glycerol gelatin suppository and granules were prepared, and their antibacterial effects were studied. 1. Study on the preparation of Glycerin Gelatin suppository and its effect on vaginitis 1.1 preparation of Glycerin-Gelatin suppository Water soluble Matrix PEG and Glycerol Gelatin; The fatty matrix is mainly semisynthetic fatty acid glyceryl ester as the matrix. The type and dosage of the matrix are screened by hot melt method, the dissolution degree of suppository and the melting time. The results showed that the properties of glycerol gelatin suppository prepared by hot melt method were stable. The quality evaluation of glycerol gelatin suppositories was carried out according to the Chinese Veterinary Pharmacopoeia (2010 Edition), including the appearance, weight difference, melting time and dissolution of the suppositories. All the items meet the requirements of China Veterinary Pharmacopoeia (version 2010), and the quality is stable. 1.3 effect of Glycerol Gelatin suppository on bacterial vaginitis: single and multiple vaginal administration of glycerol gelatin suppositories were performed in rats, and staphylococcus aureus was used to infect the vaginas of rats, and then VA suppository was used to treat the vaginitis of rats. And evaluate its efficacy. The results showed that the preparation had no vaginal irritation in rats. The total negative conversion rates of VA suppositories to staphylococcus aureus were 60%, 100%, 100% in low, middle and high dose (50100150mg Kg-1) vaginal administration, respectively. In VA suppository, the efficacy of high dose was similar to that of ornidazole suppository (100mg Kg-1). There was no significant difference (P0.05). 2. Study on preparation and antibacterial effect of ointment the W / O and O / W VA ointment were prepared by emulsion method, and the in vitro transdermal release rate of VA in the ointment was determined by high performance liquid chromatography (HPLC). The results showed that the in vitro transdermal release rates of W / O and O / W ointment for 10 h were 30% 卤0.42% and 18.45% 卤0.69%, respectively. The bacteriostatic test in vitro showed that W / O type had more obvious inhibitory effect on Staphylococcus aureus, and the stability of two kinds of ointment prepared was good. 3. Study on the preparation of granules and their Therapeutic effects on Escherichia coli diarrhea; 3.1.The preparation process of VA granules was optimized by wet granulation. The formability, moisture absorption and solubility of the granules were used as the indexes, and the results were as follows: (1) the size of the granules was higher than that of the control group. Screening the type and dosage of auxiliary materials. The results showed that the quality of the prepared granules met the requirements of China Veterinary Pharmacopoeia (2010 Edition), and the optimal prescription process was reasonable and feasible. The quality of VA granules was evaluated by wet granulation. The content of VA in granules was determined by ultraviolet spectrophotometry. The results showed that the method was simple and reliable for the determination of VA in granules by UV. Good reproducibility. Appearance properties, grain size, drying weight loss, solubility and so on meet the requirements of China Veterinary Pharmacopoeia (2010 Edition). Experimental study on the therapeutic effect of granule on coliform diarrhea in mice. Diarrhea model was established by intraperitoneal injection of pathogenic Escherichia coli in mice. Four hours later, different doses of VA granules were given intragastrically to treat diarrhea in mice. After 3 days treatment, the results showed that VA granules were effective in the treatment of coliform diarrhea.
【学位授予单位】：西南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943;R965

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