【作者】 张瑾；

【导师】 陈虹；

【作者基本信息】 天津医科大学 ， 药物化学， 2015， 硕士

【摘要】 湿疹、皮炎是常见的由多种内外因素引起的炎症性皮肤病。其特点为剧烈瘙痒,皮损多形性,有渗出倾向等。湿疹、皮炎病程长,易反复发作,但目前国内外市场上均没有可反复应用,毒副作用低的理想制剂,急需具有抗炎、抗湿疹、止痒、治疗蚊虫叮咬的中药乳膏制剂。因此我们课题组研发了复方甘草次酸湿痒霜,是一种新型的以甘草次酸(glycyrrhetinic acid,GA)为主要成分的乳膏制剂,其疗效确切,作用温和,不刺激,临床应用广泛,具有抗炎、止痒的作用,能迅速缓解由蚊虫叮咬,湿疹等引起的皮肤瘙痒及不适感,祛痒,祛痱作用明显。本课题拟进行复方甘草次酸湿痒霜质量标准及GA经皮渗透的研究。复方甘草次酸湿痒霜的研发成功,为湿疹、皮炎等皮肤病的缓解和治愈提供了纯天然成分的新外用药物。本文第一部分为复方甘草次酸湿痒霜的物理性状及微生物限度检查。根据《中国药典》2010版一部的相关规定,建立了复方甘草次酸湿痒霜的质量检测方法,包括对性状、粒度、装量差异、微生物限度、重金属和砷盐进行实验测定。实验结果显示,复方甘草次酸湿痒霜性状、粒度、装量差异、微生物限度、重金属和砷盐的检查,均符合《中国药典》2010版一部的相关要求。本文第二部分为复方甘草次酸湿痒霜的含量测定及有关物质检查。采用高效液相色谱(High Performance Liquid Chromatography,HPLC)分析法(PDA检测器)对GA的含量和有关物质进行测定。色谱柱为Agela-C18色谱柱(250mm×4.6 mm,5μm);流动相:0.1%的磷酸∶乙腈(40:60,v/v);流速:1.0 mL·min-1;检测波长:254 nm;柱温:35℃。GA在5.062 5~405μg·mL-1,(r=0.999 9)浓度范围内与峰面积呈良好的线性关系,平均回收率100.13%,(RSD=0.41%,n=9)。复方甘草次酸湿痒霜中GA含量范围为标示量的90%~110%,3批样品的总杂质含量分别为3.69%、3.90%和3.84%,实验结果均符合《中国药典》2010版一部的相关要求。该方法灵敏、准确、简便、专属性强,可作为该制剂质量控制的有效手段。本文第三部分为不同促透剂对复方甘草次酸湿痒霜中GA透皮吸收的影响。考察不同促透剂对复方甘草次酸湿痒霜中GA经皮渗透的影响。采用Franz扩散池,以离体鼠皮为屏障,选用不同组合的氮酮、冰片、薄荷醇为促透剂,在各时间段测定复方甘草次酸湿痒霜单位面积的累计渗透量。实验结果显示,各个组合的促透剂均可以不同程度地促进复方甘草次酸湿痒霜的透皮吸收效果,其促渗效果顺序为2%氮酮+2%薄荷醇+2%冰片>2%氮酮>2%氮酮+2%薄荷醇>2%氮酮+2%冰片>2%薄荷醇+2%冰片>2%薄荷醇>2%冰片。其中,氮酮与其他两种促透剂联合使用可达到最佳的透皮效果。本文进行了复方甘草次酸湿痒霜质量标准的研究,并且考察了不同促透剂对复方甘草次酸湿痒霜中GA体外透皮吸收作用的影响,为复方甘草次酸湿痒霜的进一步药效学研究打下了坚实的基础。更多还原

【Abstract】 Eczema and Dermatitis are common inflammatory dermatoses caused by various internal and external factors with symptoms of intense itching, herpes Hill pleomorphic damage and exudation tendency, etc. Eczema and dermatitis always have a long course and tend to recrudesce, but there are not satisfactory agents with low toxic and side-effects that can be used repeatedly at home and abroad so far. Given that we need a traditional Chinese cream preparation for anti-inflammatory, treatment of eczema, itching, treatment of mosquito bites. Therefore, our research group develops the compound glycyrrhetinic acid wet itch cream, the main component of which is GA. It has characteristics of accurate curative effect, gentle, no stimulation, wide spread in clinical application. Anti-inflammation and anti-pruritic effect, which enable it to quickly ease pruritus and discomfort by mosquito bites, eczema and other skin diseases. The aim of our work is to establish the quality criterion and study pereutaneous penetration in vitro of compound glycyrrhetinic acid wet itch cream. The successfully in developed preparation with natural component is a new external agent against inflammatory dermatoses, such as Eczema and Dermatitis. This paper is divided into three parts.The main content of part one is physical properties and microbial limit examination of compound glycyrrhetinic acid wet itch cream.According to the related requirements of the first part of Chinese pharmacopoeia 2010 edition, we establish the quality examination method of the preparation, which consists of characteristics, particle size, weight discrepancy, microbial limit, the content of heavy metals and arsenic salts. Through a series of examinations, the results show that characteristics, particle size, weight discrepancy, microbial limit, the content of heavy metals and arsenic salts are in line with the specifications of national pharmacopoeia.The main content of part two is about the determinations of the content and related substances in compound glycyrrhetinic acid wet itch cream.We establish a HPLC method determining the content of GA and other substances in compound glycyrrhetinic acid wet itch cream. HPLC was performed on a Agela-C18 column(250mmx4.6mm, 5μm) with mobile phase of 0.1% phosphoric acid solution–acetonitrile(40:60) at a flow rate of 1.0 m L·min-1. The detection wavelength was 254 nm and the column temperature was 35℃. There was a linear relationship between GA and peak area, when the concentration ranged from 5.0625 to 405μg·mL-1(r=0.9999), and the average recovery was 100.13%,(RSD=0.41%, n=9). The content range of GA is 90%~110% of labeled content, and the total impurity content of three samples were 3.69%, 3.90% and 3.84%, respectively. Due to its feature of sensitive, accurate, simple, and specific, the established method can be used as a reliable method for the quality control of compound glycyrrhetinic acid wet itch cream.The main content of part three is about the effect of penetration enhancer on GA percutaneous absorption.We investigate the effects of add and non-add penetration enhancer on percutaneous absorption of compound glycyrrhetinic acid wet itch cream in vitro. Using Franz disperser and excised rate skin in vitro as the cutaneous barrier, and adopting different combinations of azone, menthol and dryobalanops camphor as penetration enhancer, and 75% ethanol+25% NS as reception liquid, we determine progesterone′s unit area accumulation osmolality at different times. The different combinations of azone, menthol and dryobalanops camphor, were found to influence penetration at different extents. As followed were the influence degree ranks: 2% azone+2% dryobalanops camphor+2% menthol>2% azone>2% azone+2% menthol>2% azone+2% dryobalanops camphor>2% menthol +2% dryobalanops camphor>2% menthol>2% dryobalanops camphor. Among those, azone with two of the others had the largest penetration enhancing effect.In this paper, we revise the quality criterion for compound glycyrrhetinic acid wet itch cream and investigate the effect of different penetration enhancers on penetration enhancing effect. The metabolism studies of the GA in vitro lay a solid foundation for the future pharmacodynamics studies.更多还原