巴布剂冰辛贴镇痛效果的实验

Experiment on the analgesic effect of cataplasma bingxin paste

目的:对比观察改制后的新剂型巴布剂与传统型、其他同类产品消炎镇痛膏、通络祛痛贴、复方南星镇痛贴的镇痛效果。方法:实验于2004-03/2005-01在中山大学药物开发中心药理实验室完成。①选用健康昆明小白鼠240只,雄性,6周龄。②采用醋酸扭体法对比新原剂型的镇痛作用:选60只小白鼠,按体质量均衡原则随机分为5组,每组12只:新剂型低、中、高剂量组眼贴新剂型冰辛贴(以卡波姆、聚乙烯吡咯烷酮、聚丙稀酸钠、乙二胺四乙酸、甘油、水为基质,加入中药提取浸膏,制成亲水性巴布剂贴剂,药物成分同原剂型;由中山大学药物开发中心开发研究,汕头少林药业有限公司生产,批号:040517)1.0cm×1.0cm,1.5cm×1.5cm,2.0cm×2.0cm演,原剂型组眼贴原剂型冰辛贴(成分为大黄、蒲公英、延胡索、木香、三七、白芷、红花冰片、薄荷脑等组成;为黑膏药;由中山大学药物开发中心与汕头少林药业有限公司研制并生产,批号031215)1.5cm×1.5cm演,空白组:贴仅用水溶性基质涂布于无纺布上的贴剂1.5cm×1.5cm。③采用醋酸扭体法与同类产品对比镇痛作用:再取小白鼠60只按体质量均衡原则随机分为5组,每组12只:新剂型组(贴新剂型冰辛贴1.5cm×1.5cm)消炎镇痛膏组眼贴消炎镇痛膏(主要成分为薄荷脑、冰片、樟脑、颠茄流浸膏等,白云山制药有限公司,批号050206),贴药面积1.5cm×1.5cm演通络祛痛贴组眼贴通络祛痛贴(主要成分为当归、川芎、红花、山柰等,河南羚锐制药厂,批号041204)贴药面积1.5cm×1.5cm演,复方南星镇痛贴组外贴复方南星镇痛贴(主要成分为生天南星、生川乌、丁香、肉桂等江苏南星药业有限公司生产,批号050131),药物面积1.5cm×1.5cm,空白组:同上述“空白组”。④醋酸扭体法:于小白鼠臀背部脱毛区贴上相应的贴剂。48h后,腹腔注射7g/L醋酸,0.01mL/g,造成的腹膜炎疼痛模型,计数15min内扭体次数,并计算各药镇痛百分率眼(空白组扭体次数-实验组扭体次数)/空白组扭体次数×100%演。⑤采用温水浴甩尾法对比新原剂型镇痛效果:分组及干预措施同“醋酸扭体法”实验对比新剂型和市售同类产品镇痛效果:分组及干预措施同“醋酸扭体法”实验。在小鼠臀背部脱毛贴相应贴剂,在(49.5±0.2)℃水浴中,造成热刺激疼痛模型。以尾部回缩作为痛反应,测试贴药后1,2.5,4,6,1224,36h的甩尾潜伏期,计算热刺激疼痛抑制率眼(潜伏期-阈值)/阈值×100%演。⑥计量资料差异比较采用多因素方差分析。结果:小白鼠240只均进入结果分析。①醋酸扭体法观察结果:新剂型各剂量组和原剂型组小鼠15min扭体次数明显少于空白组(P<0.01),以新剂型高剂量组最为显著,但与原剂型组差异不明显。新剂型组及其他3种贴剂组小鼠15min扭体次数均明显少于空白组(P<0.01),镇痛百分率明显高于空白组(P<0.01),以新剂型组最明显新剂型组小鼠15min扭体次数少于其他3种贴剂组,镇痛百分率高于其他3种贴剂组,但差异不明显(P>0.05)。②温水浴甩尾法观察结果:原剂型组和新剂型各剂量组小鼠贴药后1～36h温水浴甩尾痛抑制率明显高于空白组(P<0.05～0.01)。在4～6h时抑制率最高,维持36h优于原剂型,作用随浓度增加而加强,但差异不明显。4种贴剂组热刺激疼痛抑制率均高于空白组穴P<0.05雪。虽然新剂型组热刺激疼痛抑制率高于其他3种贴剂组,但差异不明显(P>0.05)。结论:新剂型巴布剂冰辛贴镇痛效果稍强于原剂型及其他同类产品但差异不明显。

AIM： To study and compare the analgesic effect of new dose-form cataplasma bingxin paste with traditional types, other dephlogisticate and analgesic plasters, pastes of activating channels and erasing pain and Nanxing compound analgesic paste after changing. METHODS： The experiment was conducted in the Central Pharmacological Laboratory of Center for Medicine Development in Sun Yat-Sen University between March 2004 to January 2005. ①240 healthy male Kunming white mice, aged 6 months were selected, ②Acetic acid writhing method was adopted to compare the analgesic effects of new dose-form and originals： Sixty mice were selected and randomly divided into 5 groups according to the principle of balanee in body mass with 12 one in each group： low, intermediate and high dose group [mice were given of new dose-form of bingxin paste （traditional Chinese medicine was added into the stroma containing carbomer, plasdone, sodium propene acid, edathamil, glycerol and water to extract extractum and make into hydrophily new dose-form cataplasma. The components of drug were the same as original dose-form; It was studied by the Medicine Development Center of Sun Yat-Sen University, and manufactured by Shaolin Pharmaceutical Co., Ltd. in Shantou with the lot number of 040517） sized of 1.0 cm×1.0 cm, 1.5 cm×1.5 cm, 2.0 cm ×2.0 cm]. Original dose-form group [mice received bingxin paste of original dose-form （components： rheum officinale, dandelion, corydalis tuber, aucklandiae, pseudo-ginseng, angelica dehurica, carthamus tinctorious, borneol and menthol ,etc. It was a black piaster and was manufactured by the Medicine Development Center of Sun Yat- Sen University and Shantou shaolin Pharmaceutical Co., Ltd. with the lot number of 031215） 1.5 cm ×1.5 cm]. Blank group： mice only received paste of water-soluble stroma besmeared on non-spin cloth that sized of 1.5 cm×1.5 cm. ③Acetic acid writhing method was used to compare the analgesic effect with products of the same class： another 60 mice were selected and randomly divided into 5 groups according to the principle of balance in body mass with 12 mice in each group： new dose-form group （mice received new dose-form bingxi paste sized of 1.5 cm×1.5 cm）, paste for eliminating inflammation and dispelling pain group （main ingredients were menthol, camphol, camphor and extractum belladonnae liquidum, etc. made by Baiyunshan Pharmaceutical Co., Ltd. with the batch number of 050206） 1.5 cm×1.5 cm]. Paste for dredging meridian and dispelling pain group [ mice received pastes of dredging meridian and dispelling pain （ major components were angelica root, Szechwan lovage rhizome, safflower and galanga resurrectionlily rhizome, etc. made by Henan Lingrui Pharmaceutical Co., Ltd. with the lot number of 041204） 1.5 cm×1.5 cm]. Mice in the compound Nanxing analgesic paste group received compound Nanxing analgesic paste （main ingredients were raw rhizoma arisaematis, raw common monkshood mother root, cloves and cinnamon, etc. and manufactured by Jiangsu Nanxing Pharmaceutical Co. Ltd with the lot number of 050131）, medicine acreage was 1.5 cm×1.5 cm. Blank group： the same as above-mentioned ＂blank group＂. ④Acetic acid writhing method： pastes were stuck in the depilated part of hip and back in mice. After 48 hours, intraperitoneal injection of 7 g/L acetic acid was conducted at 0.1 mL/10 g to establish model of peritonitis pain, and times of writhing were counted and the analgesic percentage of all drugs were calculated [writhing times in the blank group-writhing times in the experimental group/writhing times in the blank group × 100%].⑤Lukewarm bath tail-flick method was adopt to compare with the analgesic effect of new dose-form and the origi nal： the group-division and intervention measures were the same as ＂acetic acid writhing＂ experiment. The analgesic effects of new dose-form and same-kind products in sell were compared： the group-division and intervention measures were the same as ＂acetic acid writhing＂ experilnent. The paste was stuck in the depilated part of hip and back in mice, and then mice received a bath at （49.5±0.2） ℃ to establish heat stimulated pain models. The tail contract was taken as pain response, and the tailflick latency （TFL） at 1,2.5,4,6,12,24 and 36 hours after administration were detected. The pain restraining rate of heat stimulation was calculated [（latency-threshold）/threshold×100%]. ⑥Differences in measurement data were analyzed with multiple-factor analysis of variance. RESULTS： A total of 240 mice were involved in the analysis of results. ①Observation of acetic acid writhing： the writhing times in all doses of new dose-form group and the original dose-form group within 15 minutes were significantly less than those in the blank group（P 〈 0.01）, and those in the hlgh-dose new dose-form group was the most, which was not obviously different from the original dose-form group. The writhing times of rats within 15 minutes in the new dose-form group and three other.group were remarkably less than the blank group （P 〈 0.01）, and its analgesic percentage was significantly higher.than blank group （P 〈 0.01）, that in the new dose-form group was the most significant. The writhing times of rats within 15 minutes in the new dose-form group were less than 3 otber groups, whereas the analgesic percentage was higher than other 3 groups, however the differences were no significant （P〉 0.05）. ②The result of lukewarm bath tail-flick method： at 1-36 hours after paste-sticking, the rate of lukewarm bath tail-flicking inhibition in rats of the original doseform group and new dose-form group were significantly higher than that in the blank group （P 〈 0.05-0.01）. Arid the pain-relieving rate reached the peak at 4-6 hours and lasting for 36 hours, which was better than the original dose-form. The effect became stronger with the increased concentration, while the differences were not obvious. The pain-relieving rate of heat stimulation in 4 kinds of paste group were higher than that of the blank group （P 〈 0.05）. Ahhough the pain-relieving rate of heat stimulation in the new dose-form group was higher than three others, the differences were little （P 〉 0.05）. CONCLUSION： The effect of new dose-form bingxin cataplasma paste is better than the original dose-form and other products, while the differences are not significant.