利福昔明透皮剂的制备及其药效学评价

doi:10.16431/j.cnki.1671-7236.2024.01.042

中国畜牧兽医 ›› 2024, Vol. 51 ›› Issue (1): 417-426.doi: 10.16431/j.cnki.1671-7236.2024.01.042

利福昔明透皮剂的制备及其药效学评价

张剑旭¹, 王禹霏^1,2, 徐诗瑶³, 张嘉斌^1,2, 霍雨柔^1,4, 赵琪^1,4, 李波^1,2, 杨玉洁^1,4, 王凯¹, 李乾学¹

1. 中国农业科学院长春兽医研究所, 长春 130122;
2. 吉林农业大学动物医学院, 长春 130118;
3. 通化师范学院生命科学学院, 通化 134002;
4. 长春理工大学生命科学技术学院, 长春 130022

收稿日期:2023-06-29 出版日期:2024-01-05 发布日期:2023-12-27
通讯作者: 王凯, 李乾学 E-mail:kangxiwangkai1986@163.com;lqxue@hotmail.com
作者简介:张剑旭,E-mail:longde.guxiang@163.com。
基金资助:
国家自然科学基金（32001004、31902224）

Preparation and Pharmacodynamic Evaluation of Rifaximin Transdermal Preparation

ZHANG Jianxu¹, WANG Yufei^1,2, XU Shiyao³, ZHANG Jiabin^1,2, HUO Yurou^1,4, ZHAO Qi^1,4, LI Bo^1,2, YANG Yujie^1,4, WANG Kai¹, LI Qianxue¹

1. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China;
2. College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China;
3. College of Life Science, Tonghua Normal University, Tonghua 134002, China;
4. College of Life Science and Technology, Changchun University of Science and Technology, Changchun 130022, China

Received:2023-06-29 Online:2024-01-05 Published:2023-12-27

摘要/Abstract

摘要： 【目的】研制一种给药途径方便、皮肤透过效果较好的利福昔明透皮剂用于畜禽肠道疾病治疗，并对其进行制剂学和药效学初步评价。【方法】采用紫外分光光度计法检测利福昔明浓度，采用正交设计法进行透皮剂制备试验，通过离体猪皮考察制剂体外透皮能力，以12 h单位面积累积渗透量（Q）为指标筛选处方组分，并测定制剂在40和60 ℃的存储稳定性。建立小鼠感染鼠伤寒沙门菌模型，通过对比所制透皮剂与灌胃制剂对感染模型的小鼠存活率、脏器载菌量和组织病理变化的影响，对制剂治疗效果进行评价。【结果】利福昔明透皮剂处方组成为：体系含利福昔明2%、氮酮4%、薄荷醇2%、丙酮缩甘油20%、二甲基亚砜30%、无水乙醇补至100%，该透皮剂配方的单位面积累积渗透量平均值在12 h达132.82 μg/cm²。制剂在60和40 ℃放置10 d后，药物含量分别为初始的89.78%和93.53%，较为稳定。与感染不用药组相比，透皮治疗组和灌胃治疗组的各脏器载菌量均显著降低（P<0.05）。利福昔明透皮治疗组小鼠给药后3 d的存活率（91.67%）高于灌胃治疗组（83.33%）。治疗前后鼠盲肠病理切片变化明显，与感染不用药组相比，2个治疗组的肠道黏膜下层水肿减轻，黏膜下层、肠隐窝及肠上皮层处炎性细胞浸润减少，肠绒毛杯状细胞数量增加，肠上皮完整性恢复明显，病变减轻。【结论】利福昔明透皮剂制备工艺简单、稳定性好，能透过皮肤起到较好治疗效果。

关键词: 利福昔明; 透皮剂; 药效学评价

Abstract: 【Objective】 The aim of this study was to develop a transdermal formulation of rifaximin with convenient administration and good skin penetration for the treatment of intestinal diseases in livestock and poultry, and preliminarily evaluate its formulation and efficacy.【Method】 The concentration of rifaximin was detected by ultraviolet spectrophotometer.The orthogonal design method was used in the transdermal preparation test.The in vitro transdermal ability of the preparation was investigated by isolated pig skin, and the prescription components were screened by the cumulative permeation amount (Q) per unit area of 12 h.The storage stability test was carried out at 40 and 60 ℃.A mouse model of Salmonella Typhimurium infection was established, and the prepared transdermal or gavage preparation were used to treat the infection model and evaluate the therapeutic effect by comparing the survival rate, organ bacterial load and histopathological changes.【Result】 Rifaximin transdermal preparation was as follows:The system contained rifaximin 2%, azone 4%, menthol 2%, acetone glycerol 20%, dimethyl sulfoxide 30%, and anhydrous ethanol to 100%.The average cumulative permeation amount per unit area of the formulation for 12 h was 132.82 μg/cm².After placing the preparation at 60 and 40 ℃ for 10 d, the drug content was kept at 89.78% and 93.53% of the initial value respectively, which indicated its good stability.Compared with infection without treatment group, the organ bacterial load in each organ of transdermal group and gavage group were significantly reduced (P<0.05).After 3 d of administration, the survival rate of rifaximin transdermal treatment group (91.67%) was higher than that of gavage treatment group (83.33%).The pathological changes of cecum were obvious before and after treatment.Compared with infection without treatment group, the edema of the intestinal submucosa, the infiltration of inflammatory cells in the submucosa, intestinal crypts and intestinal epithelium were reduced, the number of goblet cells in the intestinal villi was increased, the integrity of the intestinal epithelium was significantly restored, and the lesions were alleviated in the two treatment groups.【Conclusion】 The transdermal preparation of rifaximin had the advantages of simple preparation process, good stability and better therapeutic effect through skin.

Key words: rifaximin; transdermal preparation; pharmacodynamic evaluation

中图分类号:

S859.5

张剑旭, 王禹霏, 徐诗瑶, 张嘉斌, 霍雨柔, 赵琪, 李波, 杨玉洁, 王凯, 李乾学. 利福昔明透皮剂的制备及其药效学评价[J]. 中国畜牧兽医, 2024, 51(1): 417-426.

ZHANG Jianxu, WANG Yufei, XU Shiyao, ZHANG Jiabin, HUO Yurou, ZHAO Qi, LI Bo, YANG Yujie, WANG Kai, LI Qianxue. Preparation and Pharmacodynamic Evaluation of Rifaximin Transdermal Preparation[J]. China Animal Husbandry and Veterinary Medicine, 2024, 51(1): 417-426.

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利福昔明透皮剂的制备及其药效学评价

Preparation and Pharmacodynamic Evaluation of Rifaximin Transdermal Preparation

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