香柏酊外用治疗头部脂溢性皮炎（湿热证）的临床及机理研究

发布时间：2018-05-11 16:48

本文选题：临床研究 + 马拉色菌　；参考：《北京中医药大学》2016年博士论文

【摘要】：1目的通过临床观察客观评价香柏酊对头部脂溢性皮炎(湿热证)的临床疗效,确立头部脂溢性皮炎(湿热证)外用药治疗的研究规范；通过动物实验及药敏实验探讨香柏酊对脂溢性皮炎治疗的作用机理。通过测定香柏酊有效成分含量进行质量监控。为外用中药制剂治疗脂溢性皮炎的研发和推广奠定基础。2方法临床研究部分：采用完全随机平行对照单盲的方法对符合头部脂溢性皮炎(湿热证)入选标准的患者90例随机分为治疗组36例、阳性对照组36例以及阴性对照组18例。三组分别外用香柏酊、联苯苄唑溶液以及安慰剂,治疗期间均使用统一发放的洗发液,隔日洗头1次,每组均每日早晚各涂药1次,疗程为4周。治疗期间,患者均需保证规律作息,饮食清淡。分别于用药0天、14±3天、28-1-3天,痊愈者停药后28±3天进行访视,对访视节点中患者的靶皮损拍照,并且记录红斑程度、靶皮损面积、鳞屑程度、瘙痒程度以及脂溢程度积分,评价各组疗效。并于用药第28-1-3天进行靶皮损真菌学镜检或培养,评价真菌学疗效。实验研究部分：①抗炎实验：取30只小鼠,随机分成三组,每组各10只,在右耳外耳廓分别外涂香柏酊、哈西奈德以及生理盐水,采用二甲苯外涂建立右耳外耳廓炎性肿胀模型,通过观察耳片肿胀度(.两只耳片重量差值),.评价各组抗炎疗效：②止痒实验：取30只小鼠,随机分成三组,每组各1 0只,各组将右后腿剃毛后外涂香柏酊、苯海拉明以及生理盐水,将剃毛处擦伤后以浓度递增的方式外涂磷酸组织胺,建立小鼠瘙痒模型,以小鼠舔右后腿时磷酸组织胺总量为致痒阈,观察各组的止痒疗效；③抑菌实验：动物实验：取豚鼠30只,采用连续7天涂菌法建立豚鼠皮肤马拉色菌感染模型,后采用自身对照法将药物外涂于感染马拉色菌的豚鼠背部皮肤,实验共分为4组,即治疗组(采用香柏酊外用)、阳性对照组(联苯苄唑溶液外用)、阴性对照组(生理盐水外用)以及空白对照组(不外用药物),分别观察连续用药4天与连续用药7天时(随机分组,每组15只),各组的培养菌落数和真菌学治愈率。体外药敏实验；采用浓度稀释法分别检测香柏酊及联苯苄唑溶液的最小抑菌浓度(MIC值)。④通过高效液相色谱仪测定香柏酊有效成分槲皮苷及α-香附酮的含量,从而进行药物质控。3结果临床研究部分：符合方案集中各组治疗4周后,香柏酊组36例,痊愈5例,显效11例,有效16例,无效4例,愈显率44.44%,总有效率为88.89%；联苯苄唑组35例,痊愈2例,显效5例,有效17例,无效11例,愈显率20.0%,总有效率68.57%：安慰剂组16例,痊愈0例,显效1例,有效3例,无效12例,愈显率6.25%,总有效率25.0%。经统计学比较,三组总有效率有显著差异,各组间疗效均具有统计学差异(P均0.05),疗效比较：香柏酊组联苯苄唑组安慰剂组。治疗4周后,各组症状积分(靶皮损面积、红斑、鳞屑、脂溢以及瘙瘁)均较治疗前有一定改善,差异有统计学意义(P0.05),在鳞屑及瘙痒方面的改善程度,香柏酊组明显优于联苯苄唑组(P0.05),其余各症状两组改善程度无明显差异(P0.05)。各组在治疗期间均无严重不良事件发生,证明香柏酊和联苯苄唑溶液的治疗均是安全有效的。在真菌清除率方面,三组疗效差异显著(P0.01),香柏酊组和联苯苄唑组差异无统计学意义(P0.05),香柏酊组=联苯苄唑组安慰剂组。实验研究部分：在小鼠耳廓炎性肿胀实验中证实,香柏酊具有较好的抗炎作用,其作用与哈西奈德溶液相当(P0.05)；在小鼠致痒实验中证实,香柏酊具有较好的止痒作用,其作用与苯海拉明溶液相当(P0.05)；马拉色菌感染豚鼠抑菌实验证实,香柏酊具有较好的抑菌作用,连续用药7天疗效明显优于4天,但疗效不及联苯苄唑(P0.05),香柏酊连续用药4天真菌学治愈率为26.67%,连续用药7天真菌学治愈率为60%,而联苯苄唑的这一数据分别为53.33%和93.33%；香柏酊的最小抑菌浓度为70mg/ml,联苯苄唑溶液的最小抑菌浓度为78.125 μg/ml。经测定,香柏酊中有效成分槲皮苷的含量为0.1050mg/ml, α-香附酮的含量为0.0147mg/ml。4结论香柏酊治疗头部脂溢性皮炎总疗效优于联苯苄唑溶液,在抑制鳞屑及缓解瘙痒等方面效果均优于联苯苄唑。香柏酊具有较强的抗炎作用和止痒效果,抗炎作用与哈西奈德溶液相当,止痒疗效与苯海拉明相当,对糠秕马拉色菌具有良好的抑菌疗效。
[Abstract]:1 Objective To evaluate the clinical effect of Xiang Bai Tincture on seborrheic dermatitis (damp and heat syndrome) in the head and establish the study standard for the treatment of seborrheic dermatitis (damp heat syndrome) for head, and explore the mechanism of the effect of Xiang Bai Tincture on seborrheic dermatitis by animal experiment and drug sensitivity test. The clinical research part of the basic.2 method for the development and promotion of seborrheic dermatitis by external use of traditional Chinese medicine preparation: 90 cases of patients with head seborrheic dermatitis (damp heat syndrome) were randomly divided into 36 cases, 36 cases of positive control group and 18 negative control group by the complete random parallel control single blind method. In the three groups, the three groups were treated with cedar tincture, Bifonazole Solution and placebo respectively. During the treatment, the unified shampoo was used and the shampoo was washed 1 times every other day. Each group had 1 times each day and evening. The treatment period was 4 weeks. The patients were required to ensure regular rest and light diet. The drugs were used for 0 days, 14 + 3 days, and 28 + 3 after the cure was stopped. The target skin lesions in the visiting nodes were photographed, and the degree of erythema, target lesion area, scale, itching degree and the degree of seborrhea were recorded, and the efficacy of each group was evaluated. The target derma microscopic examination or culture was carried out on day 28-1-3 of the drug use. The experimental study part: (1) anti-inflammatory experiment: 30 Only mice were divided into three groups, each group was divided into three groups. 10 rats in each group were coated with cedar tincture in the right ear auricle, Hasi Ned and normal saline. The inflammatory swelling of the ear auricle outside the right ear was established by using dimethylbenzene and the swelling degree of the ears (the difference of the weight of two ears). The anti inflammatory effect of each group was evaluated: 30 mice were taken randomly. It was divided into three groups, each group was 10. After shaving, the right hind legs were shaved with cedar tincture, diphenhydramine and physiological saline. After the shaving was bruised, the phosphoric acid histamine was coated in a concentration increasing manner, and the mouse pruritus model was established. The mice were licking the right hind leg and the total amount of phosphate histamine was the pruritic threshold, and the antipruritic effect of each group was observed. Animal experiments: 30 guinea pigs were taken from the guinea pig. The guinea pig model of Malassezia infection was established by 7 days of smear method, and then the drugs were applied to the back skin of the guinea pigs infected with Malassezia by self control. The experimental group was divided into 4 groups, that is, the treatment group (using the tincture of cedar tincture), the positive control group (Bifonazole Solution external use) and the negative control group. The normal saline external use) and the blank control group (no external use medicine) were observed for 4 days of continuous medication and 7 days of continuous medication (random group, 15 in each group). The number of colonies and the cure rate of mycology in each group, in vitro drug sensitivity test, and the concentration dilution method were used to detect the minimum inhibitory concentration (MIC) of Bifonazole Solution tincture and the minimum inhibitory concentration (value). The content of quercetin and alpha - peronone in fragrant cypress tincture was determined by HPLC, and the clinical study of drug quality control.3 was carried out. After 4 weeks of treatment, 36 cases of Xiang Bai tincture group were cured, 5 cases were cured, 11 cases were markedly effective, 16 cases were effective, 4 cases were invalid, the healing rate was 44.44%, the total effective rate was 88.89%, and benzyzazole group 3 was 3. 5 cases were cured, 2 cases were cured, 5 cases were effective, 17 were effective, 11 cases were invalid, the more effective rate was 20%, the total effective rate was 68.57%: 16 cases in placebo group, 0 cases, 1 cases, 3 effective and invalid 12 cases, the total effective rate of 25.0%. was statistically significant difference between the groups (P), the curative effect was compared. After 4 weeks of treatment, the symptom scores (target lesion area, erythema, scaly, seborrhea and Sao) were improved after 4 weeks of treatment. The difference was statistically significant (P0.05), the improvement of scalar and pruritus was better than that of benzopazole group (P0.05), and the other two groups of symptoms were changed. There was no significant difference in the degree of good (P0.05). Each group had no serious adverse events during the treatment. It was proved that the treatment of cypress tincture and Bifonazole Solution were safe and effective. In the area of fungal clearance, the difference between the three groups was significant (P0.01), and the difference between the fragrant cypress tincture group and benzyzazole group was not statistically significant (P0.05), and the fragrant cypress tincture = bibenzazole group was in the group of fragrant cypress tincture = bibenzazole group. In the placebo group. Experimental study: in the mouse ear inflammatory swelling test, the fragrant cypress tincture has a good anti-inflammatory effect, its effect is similar to that of Halcinonide Solution (P0.05); in the itching experiment of mice, it is proved that the fragrant cypress tincture has a better antipruritic effect and the effect is equivalent to that of the benzhydramine solution (P0.05); Malassezia infection of guinea pigs The bacteriostasis experiment proved that the fragrant cypress tincture had better bacteriostasis effect, and the curative effect of 7 day continuous medication was obviously superior to 4 days, but the curative effect was less than P0.05, the cure rate of 4 naive bacteriology was 26.67%, the cure rate of 7 naive bacteriology was 60%, while the data of benzyzazole were 53.33% and 93.33% respectively, and the smallest cypress tincture was the smallest. The bacteriostasis concentration was 70mg/ml, the minimum inhibitory concentration of Bifonazole Solution was 78.125 g/ml., the content of quercetin in fragrant cypress tincture was 0.1050mg/ml, and the content of alpha - peronone was 0.0147mg/ml.4 conclusion the total curative effect of fragrant cypress Tincture on seborrheic dermatitis in head was better than that of Bifonazole Solution, in inhibiting the scales and alleviating pruritus. The effect is better than benzyzazole. The fragrant cypress tincture has strong anti-inflammatory and antipruritic effect. The anti-inflammatory effect is equal to that of Halcinonide Solution. The antipruritic effect is equivalent to that of diphenhydramine. It has good bacteriostasis effect for Malassezia chaff.

【学位授予单位】：北京中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R275

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