阿达帕林过氧苯甲酰凝胶剂的研制和质量研究

发布时间：2018-06-12 00:19

本文选题：阿达帕林 + 过氧苯甲酰　；参考：《湖北中医药大学》2017年硕士论文

【摘要】：痤疮(acne)作为青少年人患病率极高的皮肤病,多发生在面部、胸部、背部以及颈部,其具体的发病机理尚不明确。目前有一个观点影响了人们对痤疮发病机理的认知:除开丙酸痤疮杆菌引发的原因外,自然免疫介导也能产生炎症引发痤疮。国外学者Del和Kircik通过基因技术在亚临床皮损中检测到IL-1α和整合素的基因表达,因此我们有理由认为非炎性痤疮(开放性或闭合性粉刺)也有炎症反应的参与。据相关研究显示痤疮系一种原发性的伴随炎症症状的皮肤性疾病,炎症反应贯穿了痤疮的发病过程。基于炎症反应贯穿了痤疮的整个病程,因此除抗感染治疗外,抗炎治疗将左右痤疮治疗效果的好坏,也将成为痤疮治疗新方向。痤疮这种皮肤病虽然对人体正常的生理功能干扰较轻,但外貌上的缺陷常伴随着精神压力以及心理负担。所以,用于治疗痤疮的药物研发一直以来备受重视。本课题以抗炎效果显著的阿达帕林与具有强效杀菌能力的过氧苯甲酰为主药,以甘油、依地酸二钠、丙二醇、多库酯钠、SIMUGEL 600PHA、泊洛沙姆124、氢氧化钠为辅料研制出一种新型的复方制剂—阿达帕林过氧苯甲酰凝胶。并对其进行了以下研究:首先我们对其进行处方工艺研究:筛选出最为合适的防腐剂、润湿剂等,并对甘油、Simugel 600PHA、丙二醇的用量进行筛选。通过研究凝胶剂各项指标来决定最优的处方工艺。其次在质量研究方面,参考国家食品药品监督管理局发布的阿达帕林凝胶标准,2013版美国药典记载的过氧苯甲酰凝胶标准,我们对自制凝胶进了相关质量考察。试验过程中我们采用两种不同的色谱条件分别测定阿达帕林的有关物质与含量以及过氧苯甲酰的有关物质,采用碘量法对过氧化苯甲酰进行含量测定,并对有关物质及含量测定进行了方法学研究并建立了一系列质量检测标准。为质量控制提供了试验依据。同时,质量控制中稳定性考察不可或缺的一个部分,我们通过研究自制样品随温湿度与光强度的改变趋势来设计实验,分别从影响因素、加速试验和长期试验三个方面对阿达帕林过氧苯甲酰凝胶剂进行初步考察,实验结果显示,自制样品凝胶稳定性良好,在避光,阴凉处贮藏。最后,我们对自制样品进行了体外透皮吸收实验。结果表明:主药的渗透性能良好,且自制与市售样品的渗透性能相似。通过方差分析,判断二者的治疗效果相当。
[Abstract]:Acne acnes (Acne), as a highly prevalent skin disease in adolescents, occurs mostly on the face, chest, back and neck. The specific mechanism of acne acnes is still unclear. At present, there is a view to affect the understanding of the pathogenesis of acne: in addition to the causes caused by Acne propionate, natural immune mediated acne can also produce inflammation. Foreign scholars Del and Kircik detected the gene expression of IL-1 伪 and integrin in subclinical skin lesions by gene technique. Therefore, we can conclude that non-inflammatory acne (open or closed acne) is also involved in inflammatory reaction. According to related studies, acne is a primary skin disease with inflammatory symptoms, and inflammatory reaction is involved in the development of acne. Based on the inflammatory reaction throughout the whole course of acne, in addition to anti-infection treatment, anti-inflammatory treatment will affect the effectiveness of acne treatment, but also will become a new direction of acne treatment. Although acne, a skin disease, interferes slightly with normal physiological function, the defects in appearance are often accompanied by mental stress and psychological burden. Therefore, the research and development of the drug used to treat acne has been paid more attention. In this study, the anti-inflammatory effect of Adaphalin and strong bactericidal ability of peroxobenzoyl drug, glycerol, disodium etate, propylene glycol, A new compound preparation, adalepalin peroxy benzoyl gel, was developed by using polycuryl sodium (SIMUGEL 600 PHA, Poloxamer 124, sodium hydroxide as excipient). And the following studies were carried out: first, we studied the formulation technology: the most suitable preservatives, wetting agents, and the amount of glycerol Simugel 600PHA, propylene glycol were screened. The optimum prescription technology was determined by studying the indexes of gel. Secondly, in terms of quality research, we investigated the quality of self-made gel by referring to the Adaphalin Gel Standard published by the State Food and Drug Administration (SFDA) and the peroxobenzoyl gel standard recorded in the US Pharmacopoeia in 2013. In the course of the experiment, we used two different chromatographic conditions to determine the related substances and contents of adalpine and peroxybenzoyl, and determined the content of benzoyl peroxide by iodimetry. The methods for the determination of related substances and their contents were studied and a series of quality standards were established. It provides experimental basis for quality control. At the same time, an indispensable part of stability investigation in quality control, we design experiments by studying the changing trend of self-made samples with temperature, humidity and light intensity. The results showed that the gel prepared by ourselves was stable and stored in shade and shade. Finally, in vitro transdermal absorption experiments were carried out on the self-made samples. The results showed that the permeability of the main drug was good, and the permeability of the self-made samples was similar to that of the commercial samples. According to the analysis of variance, it was judged that the therapeutic effect of the two was equal.
【学位授予单位】：湖北中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

【参考文献】