复方硫酸新霉素温敏凝胶的制备及其对复发性口腔溃疡的作用  

Preparation of compound neomycin sulfate thermosensitive gel and its treatment of recurrent oral ulcer

作　　者：王欢[1] 李正伟 杨盟 刘振康 原永芳[1] WANG Huan;LI Zheng-wei;YANG Meng;LIU Zhen-kang;YUAN Yong-fang(Department of Pharmacy,the Ninth People’s Hospital Affiliated to the Medical College of Shanghai Jiaotong University,Shanghai 200011)

机构地区：[1]上海交通大学医学院附属第九人民医院药剂科,上海200011

出　　处：《中南药学》2022年第12期2734-2739,共6页Central South Pharmacy

基　　金：上海市科学技术委员会(No.17401900800,No.19401900400);上海交通大学医学院转化项目(No.TM201714)。

摘　　要：目的制备复方硫酸新霉素温敏凝胶,并对制备工艺、理化性质进行考察,对凝胶剂中醋酸地塞米松的含量进行测定。方法考察不同比例P407和P188的流变性能,确定温敏凝胶最优处方。选取健康SD大鼠,采用化学法诱导大鼠口腔黏膜溃疡,完成复发性口腔溃疡(ROU)造模后,将SD大鼠随机分为4组,空白组(不诱导ROU,涂抹生理盐水),模型组(诱导ROU,涂抹生理盐水),实验组(诱导ROU,涂抹复方硫酸新霉素温敏凝胶),阳性对照组(诱导ROU,涂抹复方硫酸新霉素液),连续给药20 d,记录溃疡从发生至愈合的时间,及溃疡发生的间歇时间,测定大鼠组织或血清中的CD3^(+)、CD4^(+)、CD8^(+)和CD4^(+)/CD8^(+)表达。结果确定最优处方P407∶P188为18∶2,按照最优处方制备空白凝胶基质并与药液混合得复方硫酸新霉素温敏凝胶。复方硫酸新霉素温敏凝胶能够有效缩短SD大鼠口腔黏膜溃疡面积,在给药1 d后溃疡面即有收缩趋势;给药3 d后,溃疡面积缩小;给药14 d后,溃疡面的假膜脱落,溃疡愈合。复方硫酸新霉素温敏凝胶能够促进复发性口腔溃疡大鼠外周血T淋巴细胞亚群CD3^(+)、CD4^(+)和CD4^(+)/CD8^(+)比值升高,修复口腔黏膜蛋白抗原诱导的损伤,促进口腔黏膜愈合,且较复方硫酸新霉素液有更好的治疗效果。结论复方硫酸新霉素温敏凝胶可以为复发性阿弗他溃疡的临床治疗提供一种新的、有效的药物制剂。Objective To prepare compound neomycin sulfate thermosensitive gel,observe the prescription screening,preparation process,physical and chemical properties,and determine the content of dexamethasone acetate in the gel.Methods The rheological properties of P407 and P188 with different ratios were investigated to determine the optimal formulation of thermosensitive gel.Oral mucosa ulcer was induced by chemical method in healthy SD rats.SD rats were randomly divided into four groups:blank group[without inducing recurrent oral ulcer(ROU),smearing normal saline],model group(inducing ROU,smearing normal saline),experimental group(inducing ROU,smearing compound neomycin sulfate thermosensitive gel),positive control group(inducing ROU,smearing compound neomycin sulfate solution),After the ROU modeling was completed,the drug was continuously administered for 20 days.The time from the occurrence to the healing and the interval between ulcers was recorded and the expression of CD3^(+),CD4^(+),CD8^(+)and CD4^(+)/CD8^(+)in the tissues or the serum of rats were measured.Results The optimal prescription was determined P407∶P188=18∶2.According to the optimal prescription,the blank gel matrix was prepared and mixed with the drug solution to obtain the compound neomycin sulfate thermosensitive gel.Compound neomycin sulfate thermosensitive gel effectively shortened the ulcer area of oral mucosa in SD rats,and the ulcer surface tended to shrink after 1 day of administration.After 3 days of administration,the ulcer area was reduced;after 14 days of administration,the pseudomembrane on the ulcer surface fell off and the ulcer healed.Compound neomycin sulfate thermosensitive gel increased the ratio of peripheral blood T lymphocyte subsets CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)in rats with ROU,repaired the injury induced by oral mucosal protein antigen,and promoted the healing of oral mucosa.Moreover,compound neomycin sulfate thermosensitive gel showed better therapeutic effect than its solution.Conclusion Compound neomycin sulfate therm

关 键 词：复方硫酸新霉素 温敏凝胶 复发性口腔溃疡 醋酸地塞米松 病理观察 

分 类 号：R94[医药卫生—药剂学] R96[医药卫生—药学]