牛黄上清片(体外培育牛黄)治疗复发性口腔溃疡的多中心、随机对照研究

A multicentre,randomized controlled study of bezoar supernatant tablets(in vitro cultured bezoar)in the treatment of recurrent oral ulcer

目的对比牛黄上清片(体外培育牛黄)治疗复发性口腔溃疡的临床疗效。方法选取2020年4月至2022年4月期间浙江萧山医院、杭州市萧山区中医院、南京市溧水区人民医院收治的复发性口腔溃疡患者93例为研究对象,依据随机数字表法分为西药组、牛黄上清片组和联合组,每组31例。西药组口服维生素B 2片并配合锡类散外用;牛黄上清片组口服牛黄上清片,4片/次,2次/天;联合组在西药基础上加服牛黄上清片,4片/次,2次/天,3组均连续治疗4周。比较3组的溃疡愈合速度、复发率,比较两组治疗前后视觉模拟疼痛(VAS)评分、焦虑自评量表(SAS)评分、体温变化、炎症因子[白细胞介素(IL)-10、IL-6、肿瘤坏死因子-α(TNF-α)、干扰素-γ(INF-γ)]、免疫功能指标(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))水平;对比两组的临床疗效及安全性。结果联合组的平均溃疡期及复发率显著低于西药组及牛黄上清片组,差异有统计学意义(P<0.05);治疗后,3组的VAS、SAS评分及体温均较治疗前明显降低,且联合组的VAS、SAS评分及体温均显著低于西药组和牛黄上清片组,差异有统计学意义(P<0.05),牛黄上清片组与西药组比较差异无统计学意义(P>0.05);治疗后3组IL-10、IL-6、TNF-α、INF-γ水平均较治疗前降低,其中联合组各水平降低幅度显著低于西药组和牛黄上清片组,差异有统计学意义(P<0.05),牛黄上清片组各水平高于西药组,但两组比较差异无统计学意义(P>0.05);治疗后3组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均升高,CD8^(+)均降低,其中联合组CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)高于另外两组,CD8^(+)低于另外两组,差异有统计学意义(P<0.05);但牛黄上清片组各水平与西药组比较差异无统计学意义(P>0.05)。联合组的治疗总有效率分别为96.77%,均高于西药组、牛黄上清片组的77.42%、70.97%(P<0.05),西药组、牛黄上清片组组间比较差异无统计学意义(P>0.05);3组不良反应情况均较轻,总发生率比较差异无统计学意义(P>0.05)。结论牛黄上清片对比牛黄上清片(体外培育牛黄)联合西药治疗复发性口腔溃疡疗效显著,安全性高,可促进溃疡愈合,减轻疼痛,改善机体炎症反应,并增强机体免疫功能,值得临床推广应用。

Objective To compare the clinical efficacy of Niuhuang supernatant tablets(Bezoar grown in vitro)in the treatment of recurrent oral ulcer.Methods A total of 93 patients with recurrent oral ulcer who were admitted to Zhejiang Xiaoshan Hospital,Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine,and Nanjing Lishui District People′s Hospital from April 2020 to April 2022 were selected as the research objects.According to the random number table method,they were divided into western medicine group,bezoar supernutrate group,and combination group,with 31 cases in each group.Western medicine group oral vitamin B2 tablets combined with tin powder for external use;Bezoar supernatant tablet group oral bezoar supernatant tablet,4 tablets a time,twice a day;The combined group was given bezoar supernatant tablets on the basis of western medicine,4 tablets per time,twice per day,and the three groups were treated for 4 weeks.The ulcer healing speed and recurrence rate of the three groups were compared.Visual analogue pain(VAS)score,self-rating anxiety scale(SAS)score,body temperature changes,inflammatory factors[interleukin-10(IL-10),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(INF-γ)],immune function indicators(CD3^(+),CD)before and after treatment were compared between the two groups 4+,CD8^(+),CD4^(+)/CD8^(+))levels;The clinical efficacy and safety of the two groups were compared.Results The average ulcer stage and recurrence rate of combined group were significantly lower than those of western medicine group and bezoar supernatant tablet group,and the differences were statistically significant(P<0.05).After treatment,the VAS,SAS scores and body temperature of the three groups were significantly lower than those before treatment,and the VAS,SAS scores and body temperature of the combined group were significantly lower than those of the western medicine group and the bezoar supernatant tablet group,and the differences were statistically significant(P<0.05).But there was no significant difference between the two groups(P>0.05).After treatment,the levels of IL-10,IL-6,TNF-αand INF-γin the three groups were significantly lower than those before treatment,and the levels of the combined group were significantly lower than those of the western medicine group and the bezoar supernatant tablet group,and the differences were statistically significant(P<0.05),and the levels of the bezoar supernatant tablet group were higher than those of the western medicine group,but there was no significant difference between the two groups(P>0.05).After treatment,CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)were increased,while CD8^(+)was decreased in the three groups.CD3^(+),CD4^(+)and CD4^(+)/CD8^(+)in the combined group were higher than those in the other two groups,and CD8^(+)was lower than that in the other two groups,and the differences were statistically significant(P<0.05).However,there was no significant difference in each level between bezoar supernatant tablet group and western medicine group(P>0.05).The total effective rate of the combined group was 96.77%,which was higher than that of the western medicine group and the bezoar supernatant tablet group(77.42%,70.97%),and the differences were statistically significant(P<0.05).There was no significant difference between the western medicine group and the bezoar supernatant tablet group(P>0.05).There were no significant differences in the total incidence of adverse reactions among the three groups(P>0.05).Conclusion Bezoar supernatant tablets(Bezoar grown in vitro)combined with western medicine in the treatment of recurrent oral ulcer is effective and safe,which can promote ulcer healing,reduce pain,improve inflammatory response,and enhance immune function of the body,which is worthy of clinical application.