消肿止痛液消肿、促溃疡面愈合、镇痛的有效部位筛选
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篇名: 消肿止痛液消肿、促溃疡面愈合、镇痛的有效部位筛选
TITLE:
摘要: 目的:筛选消肿止痛液具有消肿、促溃疡面愈合、镇痛的有效部位,为其二次开发为软膏剂提供参考。方法:采用D101大孔树脂分离得到消肿止痛液的水洗脱部位和20%、40%、60%、95%乙醇洗脱部位。将120只SD大鼠随机分为正常组(n=8)和造模组(n=112);正常组大鼠不作处理,造模组大鼠采用肛周皮肤注射75%冰醋酸致肛周溃疡复制大鼠痔疮模型;将96只成模大鼠随机分为模型组[空白软膏基质0.51 g/(kg·d)],阳性组[马应龙麝香痔疮膏0.51 g/(kg·d)],消肿止痛液及其水洗脱部位和20%、40%、60%乙醇洗脱部位的高、低剂量组[按生药计给药剂量均分别为8.34、2.78 g/(kg·d),均制成含药软膏],每组8只;肛周涂抹给药,每天给药2次,连续给药7 d;观察给药第3、7天大鼠肛周局部症状以及给药第7天大鼠肛周局部黏膜组织病理形态并分别进行评分,考察各洗脱部位的消肿、促溃疡面愈合作用。分别取120只ICR小鼠随机分为模型组[空白软膏基质1.03 g/(kg·d)]、阳性组[马应龙麝香痔疮膏1.03 g/(kg·d)]和消肿止痛液及其各洗脱部位的高、低剂量组[按生药计均分别为16.65、5.55 g/(kg·d),均制成含药软膏],每组10只;经皮给药,每天给药2次,连续给药3 d;末次给药30 min后,分别通过醋酸扭体实验检测小鼠的扭体潜伏时间、15 min扭体次数以及热板致痛实验检测小鼠的痛阈值,考察各洗脱部位的全身和局部镇痛作用。结果:在消肿、促溃疡面愈合考察实验中,与正常组比较,模型组大鼠在给药第3、7天肛周局部症状评分以及在给药第7天肛周局部黏膜组织病理评分均显著升高(P<0.01);与模型组比较,阳性组和40%乙醇洗脱部位高、低剂量组大鼠上述评分均显著降低(P<0.05或P<0.01),20%乙醇洗脱部位高剂量组大鼠在给药第3、7天以及60%乙醇洗脱部位组大鼠在给药第7天肛周局部症状评分显著降低(P<0.05)。在镇痛考察实验中,与模型组比较,阳性组和40%乙醇洗脱部位高、低剂量组以及60%乙醇洗脱部位高剂量组小鼠的扭体潜伏时间显著缩短、15 min扭体次数均显著减少(P<0.05或P<0.01),20%乙醇洗脱部位高剂量组小鼠扭体潜伏时间显著缩短(P<0.05);阳性组、40%乙醇洗脱部位高、低剂量组小鼠给药后痛阈值显著升高(P<0.05或P<0.01)。结论:消肿止痛液40%乙醇洗脱部位具有较好的消肿、促溃疡面愈合和镇痛作用。
ABSTRACT: OBJECTIVE: To screen active fractions of Xiaozhong zhitong lotion that are able to reduce swelling, promote ulcer healing and analgesia, and to provide reference for it’s secondary development of ointment preparation. METHODS: Water elution fraction and 20%, 40%, 60%, 95% ethanol elution parts were separated by D101 macroporous resin from Xiaozhong zhitong lotion. 120 SD rats were randomly divided into normal group (n=8) and modeling group (n=112). Rats in the normal group were not treated. Hemorrhoids model was established in the model group by injecting 75% glacial acetic acid into the perianal skin to induce perianal ulcer. 96 model rats were randomly divided into model group [blank ointment matrix 0.51 g/(kg·d)], positive group [Mayinglong ointment, 0.51 g/(kg·d)], high-dose and low-dose groups of Xiaozhong zhitong lotion and it’s water elution fraction and 20%, 40%, 60% ethanol elution parts [8.34, 2.78 g/(kg·d) by crude drug, all make into containing drug ointment], with 8 rats in each group. The periphery of the anus was smeared with relevant medicine, twice a day, for consecutive 7 d. The local symptoms around the anus of rats 3 and 7 days after administration and the pathological morphology of the local mucosa around the anus of rats 7 days after administration were observed and scored respectively. The effects of each elution part for reducing swelling and promoting ulcer healing were investigated. 120 ICR mice were randomly divided into model group [blank ointment matrix 1.03 g/(kg·d)], positive group [Mayinglong ointment 1.03 g/(kg·d)], high-dose and low-dose groups of Xiaozhong zhitong lotion and it’s each elution part [16.65, 5.55 g/(kg·d) by crude drug, all make into containing drug ointment], with 10 mice in each group. Transdermal administration, twice a day, for consecutive 7 d. After 30 min of last administration, the latency time and 15 min writhing times of mice were detected by designing acetic acid writhing test; pain threshold of mice was determined by hot-plate pain test so as to investigate systemic and local analgesic effects of each elution part. RESULTS: In the detumescence and ulcer healing test, compared with normal group, the score of local symptoms around anus at 3rd and 7th day of administration as well as pathological score of hemorrhoids local mucosa were increased significantly in model group (P<0.01). Compared with model group, above scores of positive group, 40% ethanol elution high-dose and low-dose groups were decreased significantly (P<0.05 or P<0.01). The scores of local symptoms around anus in 20% ethanol elution part high-dose group at 3rd and 7th day after medication as well as 60% ethanol elution part group at 7th day after medication were decreased significantly (P<0.05). In analgesia test, compared with model group, writhing latency time was shortened significantly and 15 min writhing times was decreased significantly in positive group, 40% ethanol elution part high-dose and low-dose groups as weel as 60% ethanol elution part high-dose group (P<0.05 or P<0.01); writhing latency time of 20% ethanol elution part high-dose group was shortened significantly (P<0.05). Pain threshold of mice was increased significantly in positive group, 40% ethanol elution part high-dose and low-dose groups after medication (P<0.05 or P<0.01). CONCLUSIONS: The 40% ethanol elution part from Xiaozhong zhitong lotion is the effective part that can reduce swelling, promote ulcer healing and analgesia.
期刊: 2019年第30卷第13期
作者: 王银洁,刘本臣,刘军,宫凯敏,赛纪虎,张久存,王宏伟
AUTHORS: WANG Yinjie,LIU Benchen,LIU Jun,GONG Kaimin,SAI Jihu,ZHANG Jiucun,WANG Hongwei
关键字: 消肿止痛液;有效部位;消肿;促溃疡面愈合;镇痛;大鼠;小鼠
KEYWORDS: Xiaozhong zhitong lotion; Active part; Reducing swelling; Promoting ulcer healing; Analgesia; Rat; Mice
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