盐酸米诺环素络合物温敏凝胶的制备及初步评价

doi:10.16431/j.cnki.1671-7236.2022.12.033

摘要/Abstract

摘要： 【目的】试验旨在制备一种能在局部递送盐酸米诺环素的络合物温敏凝胶。【方法】将盐酸米诺环素与Ca²⁺形成的络合物装载入泊洛沙姆407（P407）与泊洛沙姆188（P188）制备形成的温敏凝胶中，对其温敏性、表征结构、药物含量、稳定性、体外释放效果及抗菌性能进行研究。【结果】本研究制备的盐酸米诺环素温敏凝胶，在其组方为每50 mL凝胶中含米诺环素0.25 g、P407 8 g、P188 1.5 g、CaCl₂ 0.01 g、乙酸调pH至4.0±0.2、其余量为去离子水时，外观性状显示为淡黄色澄清溶液，透明度均匀，无沉淀及药物析出，温敏性能良好（31℃即可发生胶凝）；扫描电镜下可见该凝胶形成的网格孔洞结构致密且分布均匀；平均粒径为11.5 nm，Zeta电位为－3.8 mA；体外释放药物时间长达48 h，与原料药相比明显延长；在抗菌性能检测中，与原料药相比，同浓度盐酸米诺环素络合物温敏凝胶的抑菌能力没有降低，且体外抑菌时间明显延长，抑菌效果良好。【结论】本研究成功制备了一种盐酸米诺环素络合物温敏凝胶，通过模拟体外释放试验及体外抑菌曲线表明该凝胶能显著延长药物作用时间，提高药物利用率，可为临床使用盐酸米诺环素提供一种新的给药方式。

关键词: 温敏凝胶; 盐酸米诺环素; 离子配对络合; 抗菌效果

Abstract: 【Objective】 The aim of this experiment was to prepare a complexed temperature-sensitive gel capable of local delivery of minocycline hydrochloride.【Method】 Minocycline hydrochloride complexes formed with calcium ions were loaded into a temperature-sensitive gel formed by poloxamer 407 (P407) and poloxamer 188 (P188). Its temperature sensitivity, characterized structure, drug content, stability, in vitro release effect and antibacterial properties were then investigated.【Result】 The temperature-sensitive gel of minocycline hydrochloride complex was prepared [JP2]with the formula of minocycline 0.25 g, P407 8 g, P188 1.5 g, CaCl₂ 0.01 g, [JP]acetic acid adjusted to pH 4.0±0.2 and deionized water in 50 mL of gel, and the appearance of minocycline hydrochloride complex temperature-sensitive gel showed a light yellow clarified solution with uniform transparency.The temperature-sensitive performance was good (gelling occurred at 31 ℃), the grid of pores formed by the gel was dense and uniformly distributed, the average particle size was 11.5 nm and the zeta potential was -3.8 mA, and the in vitro release time was up to 48 h, which was significantly longer compared with that of the raw materials.In the antibacterial performance test, the concentration of minocycline hydrochloride complex was the same as that of the raw materials.In the antibacterial performance test, the inhibition ability of minocycline hydrochloride complex warming gel did not decrease, and the antibacterial time in vitro was longer compared with that of the raw materials, the inhibition effect was good.【Conclusion】 In this study, a temperature-sensitive gel of minocycline hydrochloride complex was successfully prepared.The simulated in vitro release test and in vitro inhibition curve showed that the gel could significantly prolong the drug action time and improve the drug utilization, providing a new way of drug delivery for the clinical use of minocycline hydrochloride.

Key words: temperature-sensitive gel; minocycline hydrochloride; ion-pairing complexation; antibacterial effect

中图分类号:

S859

王天扬, 马蓓, 丁泽, 董天帧, 刘俊峰. 盐酸米诺环素络合物温敏凝胶的制备及初步评价[J]. 中国畜牧兽医, 2022, 49(12): 4854-4865.

WANG Tianyang, MA Bei, DING Ze, DONG Tianzhen, LIU Junfeng. Preparation and Preliminary Evaluation of Minocycline Hydrochloride Complex Temperature-sensitive Gel[J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(12): 4854-4865.

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