Characterization and In vivo Evaluation of Polymorphic Valnemulin Hydrogen Fumarate.

Zhu Xinle, Zhang Li, Li Jian, Zhao Hui, Gu Jinhua, Wang Hejia
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Abstract

Aims: In the present study, a valnemulin hydrogen fumarate prodrug was characterized, its stability was compared with valnemulin hydrochloride, and the efficacy was evaluated in Actinobacillus pleuropneumoniae-induced pneumonia in mice.

Method: Optical microscopy, X-ray powder diffraction, infrared spectroscopy, and hydrogen nuclear magnetic resonance spectroscopy were used to study the physical and chemical properties of the prodrug. The thermal stability was investigated in comparison with valnemulin hydrochloride to improve the preparation process of valnemulin hydrogen fumarate soluble powder and maximize its drug effect. Additionally, the efficacy of valnemulin hydrogen fumarate was evaluated in a challenge-treatment trial in mice using an in vitro antimicrobial susceptibility test.

Results: The valnemulin hydrogen fumarate had high crystallinity. After light irradiation for 20 days, valnemulin hydrogen fumarate did not degrade, whereas valnemulin hydrochloride did. These results showed that the valnemulin hydrogen fumarate was stable. At the same dose in drinking water, the valnemulin hydrogen fumarate was more effective than the reference drug (tiamulin fumarate) in an Actinobacillus pleuropneumoniae challenge-treatment trial.

Conclusion: Valnemulin hydrogen fumarate shows excellent potential for application as a veterinary drug.

多态富马酸缬氨胆碱的特性和体内评估
目的:本研究对富马酸氢缬氨噻肟原药进行了表征,比较了其与盐酸缬氨噻肟的稳定性,并评估了其在胸膜肺炎放线杆菌诱导的小鼠肺炎中的疗效:方法:利用光学显微镜、X 射线粉末衍射、红外光谱和氢核磁共振光谱研究了原药的物理和化学特性。与盐酸缬奈莫林相比,研究了其热稳定性,以改进富马酸缬奈莫林可溶性粉末的制备工艺,最大限度地发挥其药效。此外,还利用体外抗菌药敏感性试验对富马酸缬奈莫林进行了小鼠挑战治疗试验,以评估其疗效:富马酸缬奈莫林的结晶度很高。在光照 20 天后,富马酸缬奈莫林没有降解,而盐酸缬奈莫林却降解了。这些结果表明富马酸氢缬氨醇是稳定的。在胸膜肺炎放线杆菌挑战治疗试验中,富马酸缬奈莫林在饮用水中的相同剂量下比参考药物(富马酸替莫林)更有效:结论:富马酸缬氨噻肟酯显示出作为兽药应用的巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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