续骨油湿敷剂的抗炎镇痛作用及安全性评价

Xugu Oil Moist Compress: Anti-inflammatory and analgesic effects and safety evaluation

目的通过动物实验评价续骨油湿敷剂的抗炎、镇痛作用及其安全性。方法SD大鼠50只,随机分为对照组、扶他林组、续骨油湿敷剂高、中、低剂量组(n=10),注入蛋清前后各涂药1次,在注入蛋清前及注入后0.5、1、2、4、6h观察大鼠肿胀肢体厚度,以研究续骨油湿敷剂对蛋清所致大鼠足趾肿胀的影响,评价其抗急性炎性反应作用。NIH小鼠100只,随机分为二甲苯致炎实验组、冰醋酸扭体实验组,各组再分别分为对照组、扶他林组、续骨油湿敷剂高、中、低剂量组(n=10),每日给药1次,连续3d。二甲苯致炎实验组在末次给药1h后涂抹二甲苯以致炎,30min后处死小鼠研究续骨油湿敷剂对二甲苯所致小鼠耳廓肿胀的影响,评价其抗炎作用;醋酸扭体实验组在末次给药1h后,腹腔注射醋酸0.2ml/只,观察15min内小鼠的扭体情况以评价续骨油湿敷剂对冰醋酸所致小鼠扭体的镇痛作用。背部去毛的白化豚鼠32只,随机分为单次给药组和多次给药组,各组又分别分为完整皮肤组、破损皮肤组(n=8)。单次给药组用药24h洗除药液,分别于1、24、72h观察皮肤;多次给药组每日给药3次,连续7d,停药后观察皮肤7d,以研究续骨油湿敷剂对豚鼠完整及破损皮肤的影响,评价其外用的安全性。结果与对照组相比,扶他林组、续骨油湿敷剂高、中、低剂量组在给药后0.5、1h大鼠足趾肿胀度降低(均P<0.05)。与对照组相比,扶他林组、续骨油湿敷剂高、中剂量小鼠耳廓肿胀度降低(均P<0.05)。与对照组相比,扶他林组、续骨油湿敷剂高、中、低剂量组扭体次数降低(均P<0.05)。单次给药实验中完整皮肤组及破损皮肤组豚鼠在涂药后1、24、72h均存活,其饮食、行为活动、眼和黏膜、精神状态、粪便及分泌物均正常,皮肤无明显红斑、无水肿现象。多次给药实验中,完整皮肤组及破损皮肤组豚鼠在用药的7d及停药观察7d中均存活,其饮食、行为活动、眼和黏膜、呼吸及精神状态、粪便及分泌物均正常,受药部位皮肤无色素沉着、出血点、皮肤粗糙、皮肤菲薄等情况,且破损部位已结痂。结论续骨油湿敷剂具有较明显的抗炎、镇痛的功效,且外用于皮肤未见明显的局部和全身过敏反应。

Objective To evaluate the anti-inflammatory and analgesic effects and the safety profiles of Xugu Oil Moist Compress (XOMC) via animal experiments. Methods Fifty SD rats were randomly divided into control group, Voltaren group and XOMC high-, medium- and low-dose groups (n=10 each). The animals received skin application of corresponding agents before injection of egg white. The thickness of the swollen rat limbs was measured at baseline and at 0. 5, 1, 2, 4, and 6 h after the injection, such that the effect of XOMC on egg white induced toe swelling in rats and its action against acute inflammation were evaluated. A total of 100 NIH mice were randomly divided into the xylene-induced inflammation group and glacial acetic acid writhing group. Each of these two groups was further divided into the control group, Voltaren group and XOMC high-, medium- and low-dose groups (n=10 each) to be applied with corresponding agents once daily for 3 consecutive days. In the xylene-induced inflammation group, the mice were applied with xylene to induce inflammation at 1 h after the last skin administration, and sacrificed 30 min later, such that the effect of XOMC on xylene-induced auricle swelling and its anti-inflammatory action were evaluated. In acetic acid writhing group, the mice were intraperitoneally injected with acetic acid (0.2 ml each) at 1 h after the last skin administration, such that the writhing of the mice within 15 min following the injection, and the analgesic effect of XOMC on glacial acetic acid induced writhing were determined. Thirty-two back-shaved albino guinea pigs were randomized into the single-dose group and the multiple-dose group. Each of these two groups was divided into the skin-intact group and skin-damaged group (n=8 each). The mice in the single-dose group were washed off the topical XOMC at 24 h after application, and observed for the skin condition at 1, 24, and 72 h. The mice in the multiple-dose group received skin administration of XOMC 3 times daily for 7 days, and were subject to a 7-day observation of the skin condition after discontinuation of XOMC, such that the effect of XOMC on the intact and damaged skin of guinea pigs, and its safety for external use were evaluated. Results Compared with the control group, the toe swelling of the rats in the Voltaren group, XOMC high-, medium- and low-dose groups was milder at 0.5 and 1 h after administration (all P<0.05). Compared with the control group, the severity of auricle swelling in mice of Voltaren group, XOMC high- and medium-dose groups was milder (all P<0.05). Compared with the control group, the number of writhing in mice of the Voltaren group, XOMC high-, medium- and low-dose groups was fewer (all P<0.05). In the single-dose experiment, all the guinea pigs in the skin-intact group and skin-damaged group survived 1, 24, and 72 h after application, and were normal in dieting, behavioral activities, eyes and mucosa, mental state, feces and secretions;inspection of XOMC-applied site did not reveal significant erythema and edema of the skin. In the multiple-dose experiment, all guinea pigs in the skin-intact group and skin-damaged group survived 7 days of XOMC treatment and 7-day observation after discontinuation, and were normal in dieting, behavioral activities, eye and mucosa, breathing, mental state, feces and secretions;inspection of XOMC-applied site did not reveal significant pigmentation, petechia, roughening or thinning of the skin;all damaged sites of the skin had been covered with incrustation. Conclusion XOMC exhibits obvious actions in anti-inflammation and analgesia, and does not elicit topical or systemic skin allergies in external use.